NNZ-2566 in Rett Syndrome and Autism Spectrum Disorders Role and Update

Size: px
Start display at page:

Download "NNZ-2566 in Rett Syndrome and Autism Spectrum Disorders Role and Update"

Transcription

1 NNZ-2566 in Rett Syndrome and Autism Spectrum Disorders Role and Update 1

2 Overview The natural growth factor IGF-1 is broken down in the body to IGF-1[1-3] NNZ-2566 is an analogue of IGF-1[1-3] developed by Neuren Pharmaceuticals Ltd. NNZ-2566 has enhanced oral availability and a pharmaceutical profile suitable for investigation in autism spectrum disorders. Autism, Rett Syndrome and Fragile X Syndrome: disorders of synaptic connectivity involving neuroinflammation IGF-1[1-3] and NNZ-2566 have benefit in models of Rett Syndrome and Fragile X Syndrome Clinical study in Rett Syndrome is underway Clinical study in Fragile X Syndrome is being planned 2

3 IGF-1, IGF-1[1-3] and NNZ

4 IGF-1 and IGF-1[1-3] IGF-1 is essential for brain development, widely expressed in the CNS, upregulated following brain injury Naturally occurring neurotrophic factor one of the brain s self-repair mechanisms IGF-1[1-3] is believed to be the active neuroprotective moiety in response to injury IGF-1 [1-3]appears to upregulate IGF-1 in the brain, enhance IGF1R phosphorylation and expression of synaptic markers 4

5 IGF-1[1-3] Mechanism of Action IGF-1[1-3]: Reduces cytokines 2 and neuroinflammatory markers in brain Activates Akt-mToR pathway in microglia Increases markers of presynaptic and postsynaptic synapses Activates Akt-mToR pathway in mecp2 knockout mouse model of Rett Syndrome IGF[1-3] reduces number of microglia in hippocampus following hypoxia ischemia in rat brain Casandra et al (2011) Guan et al (2004) Neuropharmacology 47:892 Corvin et (2012) Neurosci Lett. 520:51 Tropea et al. (2009) PNAS 106:2029 5

6 NNZ-2566 (oral formulation) NNZ-2566 is a (1-3)IGF-1 analog Longer half-life Crosses blood brain barrier Orally available (45-50%) Conventional solution phase synthesis Validated manufacturing process Excellent stability Targets: inflammation, synaptic function, and microglial activation Dose-dependent effects in animal models with delayed administration No clinical toxicity in rats at highest dose tested for 28 days No SAEs, no clinically significant AEs in Phase I trial up to 100 mg/kg b.i.d. x 5 days Formulated with water Peak plasma level at 2 hours with or without food Creates opportunities for chronic dosing 6

7 Autism, Rett Syndrome and Fragile X Syndrome 7

8 Synapsopathy in ASDs Altered synapses in idiopathic (non-syndromal) and syndromal autism Functional consequences: impairments in synaptic plasticity, excitatory/inhibitory imbalance, and disrupted neuronal synchrony Hutsler and Zhang (2010) Brain Res 1309:83 Irwin et al (2000) Cerebral Cortex 10:1038 Chapleau et al (2009) Neurobiol Dis 35:219 8

9 Synapsopathy in ASDs Dolan and Bear, J Neurodev Disord 2009 June; 1(2):

10 ASDs: impaired neuronal network performance Kelleher and Bear, Cell 135, October 31, 2008

11 Neuroinflammation in ASDs Microglia and astroglia are activated in brain in autism Fragile X Syndrome astrocytes can institute neuronal phenotype, and wild type astrocytes can rescue Fragile X Syndrome phenotype Wild type microglia rescue Rett Syndrome phenotype Vargas et al (2005) Ann Neurol. 57:67 Jacobs et al (2010) BMC Neurosci. 11:132 Maezawa and Jin (2010) J Neurosci. 30:

12 Cytokines in ASDs Cytokines are cell signalling molecules produced by immune system cells including microglia Interleukin-6 is an example: Interleukin-6 may be involved in autism, Fragile X Syndrome and Rett Syndrome Interleukin-6 can activate microglia IL-6 induces changes in dendritic spine density, alters neuronal adhesion and migration, causes excess in excitatory synapses, and reduces social interaction in an animal model of autism Ashwood et al (2011) Brain Behav Immun. 25:40 Ashwood et al (2010) Brain Behav Immun. 24:898 De Filippis et al (2012) Neuropsychopharmacology 37:1152 Krady et al (2008) J Neurosci Res. 86:1538 Wei et al (2012) Biochim Biophys Acta. 1822:831 Wei et al (2011) J Neuroinflammation 8:52 12

13 Glia-neuron interactions 13 Blank and Prinz, Glia 61:62-70 (2013)

14 Neuronal Transcriptional Control, Growth and Survival: Cytokines and Growth Factors in Fragile X Syndrome Effect of NNZ-2566 NNZ-2566 Believed to attenuate aberrant cytokine levels IL-6 GP130 Activated Microglia NNZ-2566 Believed to restore normal microglia function; perhaps through normalizing autocrine homeostasis Caspase-8 Bid Bax Caspase-3 STAT3 JAK3 mtor PI3K Akt NF- κb Protein Synthesis Regulation Normalised Dendritic Growth NNZ-2566 Reverses Akt in fmr1 KO _ mice Bad Ras MEK ERK NNZ-2566 Reverses ERK in fmr1 KO mice Normal Dendritic Pruning Cell Death / Apoptosis

15 Neuronal Transcriptional Control, Growth and Survival : Cytokines and Growth Factors in Rett Syndrome Effect of NNZ-2566 NNZ-2566 Believed to attenuate aberrant cytokine levels IGF-1(1-3) reported to increase IGF-1 receptor activation; may help reverse impaired Akt/mTOR activation in absence of MeCP2 IL-6 GP130 Restoration of Microglia NNZ-2566 Hypothesized to restore normal function of microglia. Increased microglial Atf3 is reported, this would reduce local IL-6 and TNF-α, attenuating autocrine activation. IGF-1(1-3) reported to activate Akt in microglia Caspase-8 Bid Bax Caspase-3 STAT3 JAK3 mtor PI3K Akt NF- κb _ Bad Ras MEK ERK Increase in total brain pakt reported mice following IGF-1(1-3) Protein Synthesis Regulation Improved Dendritic Growth Improved Dendritic Pruning Cell Death / Apoptosis

16 Mechanism of Action Summary NNZ-2566 is not a direct agonist of the IGF-1 receptor Traumatic brain injury Microglial activation and cytokine release stimulates pro-apoptotic pathways NNZ-2566 reduces neuroinflammation and apoptosis Fragile X Syndrome Activation of astroctyes induces Fragile X Syndrome neuronal phenotype, potentially via induction of RAS-MEK-ERK and PI3K-Akt-mToR pathways NNZ-2566 reverses neuroinflammation and Akt / ERK activation Rett Syndrome Impaired passive sentinel function of microglia related to PI3k-Akt-mToR function NNZ-2566 reverses Akt dysfunction normalizing microglial support of synaptic function 16

17 Effects on cytokines in brain injury 17

18 Normalized mrna level Time - Course of Gene Expression (qrt-pcr) IL-1b Sham 1hr 4hr 12hr 24hr 72hr 7ds IL-6 # # Sham PBBI PBBI+NNZ-2566 Sham 1hr 4hr 12hr 24hr 72hr 7ds J Neuroinflammation (2009) # # Time Post-PBBI TNF-a 1 1 E-selectin # # # Sham 1hr 4hr 12hr 24hr 72hr 7ds # Sham 1hr 4hr 12hr 24hr 72hr 7ds 18 #

19 Effects in Fragile X Syndrome model 19

20 Rescue of dendritic spines fmr1 KO mouse neurons show increased numbers of dendritic spines NNZ-2566 in the concentration range 0.5 to 50 nm dose dependently reduces excess spine number 20

21 Open Field The open field is an exposed space in which movement can be tracked. During exposure to the open field mice will habituate to the environment and thus explore less, decreasing the amount movement they show over time. The present experiment records movement and rearing during an initial exposure, during a second exposure after 10 minutes and during a third exposure after 24hours. Failures to reduce locomotion or rearing at 10 minutes and 24 hours indicate deficits in short and long term memory, respectively. A variety of measures can be collected in the open field locomotor activity and rearing are commonly reported

22 Rears / 3 min Open Field Rearing 35 Wild Type Vehicle 30 Wild Type NNZ p < 0.01 p < 0.01 fmr1 KO Vehicle fmr1 KO NNZ NS p < 0.01 N = 10 per group 10 NS 5 NS 0 0 Trial 1 Trial 2 Trial 3 fmr1 KO mice show increased activity NNZ-2566 has no effect in Wild Type mice, but significantly reduces rears in fmr1 KO mice fmr1 KO mice do not show habituation at 10 min (short term memory deficit) Thus during the short term and long term memory tests, NNZ-2566 treated fmr1 KO mice do not differ from controls

23 Elevated Plus Maze Time Spent The elevated plus maze has two open and two closed arm, raised above floor height. The open arms are more exposed and therefore create more anxiety in the mice. Mice therefore spend more time in the closed arms and visit them more. Measures taken include time spent in the arms and center of the maze, and number of arm entries

24 TimeSepnt Open Arm (sec) TimeSepnt Center (sec) TimeSepnt Closed Arm (sec) Elevated Plus Maze Time Spent NS NS NS p < p p < < p < p < 0.05 NS p < Vehicle NNZ-2566 Vehicle NNZ-2566 Wild Type frm1 KO N = 10 per group NS p < Vehicle NNZ-2566 Vehicle NNZ-2566 Wild Type frm1 KO p < 0.05 p < p < 0.01 Vehicle NNZ-2566 Vehicle NNZ-2566 Wild Type frm1 KO For time spent in both Open and Closed arm, fmr1 KO mice show a significant difference to Wild Type controls, as well as time spent in the center This reflects hyperactivity in the fmr1 KO mice, which spend much more time transiting the maze, compared to Wild Type mice, who remain in the closed arms This effect is significantly reversed following treatment with NNZ-2566

25 Social Behavior Bouts of Sniffing p < p < p < 0.01 NS Trial 1 Trial 1 Trial 1 Trial 1 Vehicle NNZ-2566 Vehicle NNZ-2566 Wild Type frm1 KO N = 10 per group fmr1 KO mice engage in significantly more bouts of sniffing compared to Wild Type mice NNZ-2566 has no significant effect in Wild Type mice After NNZ-2566 administration to fmr1 KO mice, this group is not significantly different to NNZ-2566 Wild Type mice i.e. NNZ-2566 normalizes the abnormalities in social behavior seen in fmr1 KO mice

26 Tests Weight (mg) Macro-orchidism p < p < NS NS Vehicle NNZ-2566 Vehicle NNZ-2566 Wild Type fmr1 KO fmr1 KO mice show an increase in testis weight, as do human Fragile X Syndrome patients NNZ-2566 has no significant effect in Wild Type mice After NNZ-2566 administration to fmr1 KO mice, testis weight is not significantly different from controls

27 Ras-Mek-Erk Pathway Vehicle NNZ-2566 Vehicle NNZ-2566 N = 4 per Group Vehicle NNZ-2566 Vehicle NNZ-2566 Overall levels of ERK are unchanged in the brain in fmr1 KO mice However, activation of ERK, as indexed by levels of phosphorylated ERK, is increased This activation is normalized by treatment with NNZ-2566 NNZ-2566 may also increase total ERK levels in fmr1 KO mice

28 Akt-Pathway pakt Vehicle vehicle NNZ-2566 NNZ WT KO WT KO AKT N = 4 per Group Vehicle NNZ-2566 Activation of Akt, as indexed by levels of phosphorylation, is increased This activation is normalized by treatment with NNZ-2566

29 Effects in Rett Syndrome model 29

30 Pharmacological Reversal of Phenotype IGF-1[1-3] reverses phenotype MECP2 mouse Tropea et al

31 NNZ-2566 Rett Syndrome / Fragile X Syndrome Recruitment into Phase II clinical trial in Rett Syndrome is underway 48 subjects; 2 doses plus placebo; 14 day follow-up Adolescents and adults Subjects will have baseline assessments of EEG, cardiac and respiratory rhythms, and functional status Focus on safety and signals of efficacy Large market opportunity Significant unmet need; no marketed therapeutic Symptoms amenable to treatment Potential for disease modification? Potential gateway to autism Fragile X Syndrome study planning underway 31

32 Summary NNZ-2566 shows efficacy in pre-clinical models of: Traumatic brain injury Fragile X Syndrome Rett Syndrome Efficacy accompanied by: Decrease in microglial activation Decrease in production of inflammatory cytokines Normalization of Akt and ERK activation profiles Clinical studies now underway 32

NNZ Rationale for use in Autism Spectrum Disorders

NNZ Rationale for use in Autism Spectrum Disorders NNZ-2566 Ratinale fr use in Autism Spectrum Disrders 1 Overview Autism: a disrder f synaptic cnnectivity invlving neurinflammatin Bth synaptic cnnectivity and neurinflammatry prcesses may invlve the PI3K-Akt-mTR

More information

For personal use only

For personal use only Investor Presentation 25 November 2016 1 Forward looking statements This presentation contains forward looking statements that involve risks and uncertainties. Although we believe that the expectations

More information

Investor Presentation. 3 April 2017

Investor Presentation. 3 April 2017 Investor Presentation 3 April 2017 1 Forward looking statements This presentation contains forward looking statements that involve risks and uncertainties. Although we believe that the expectations reflected

More information

Reversing the Effects of Fragile X Syndrome

Reversing the Effects of Fragile X Syndrome CLINICAL IMPLICATIONS OF BASIC RESEARCH Paul J. Lombroso, M.D., Marilee P. Ogren, Ph.D. Assistant Editors Reversing the Effects of Fragile X Syndrome MARILEE P. OGREN, PH.D., AND PAUL J. LOMBROSO, M.D.

More information

NNZ-2566, a Novel Analog of (1 3) IGF-1, as a Potential Therapeutic Agent for Fragile X Syndrome

NNZ-2566, a Novel Analog of (1 3) IGF-1, as a Potential Therapeutic Agent for Fragile X Syndrome Neuromol Med (2015) 17:71 82 DOI 10.1007/s12017-015-8341-2 ORIGINAL PAPER NNZ-2566, a Novel Analog of (1 3) IGF-1, as a Potential Therapeutic Agent for Fragile X Syndrome Robert M. J. Deacon Larry Glass

More information

Research Development: Bedside to Bench and Back

Research Development: Bedside to Bench and Back Research Development: Bedside to Bench and Back Matt Bellizzi, MD PhD Department of Neurology University of Rochester School of Medicine and Dentistry Rochester, NY "I can walk down the hall just fine,

More information

Neuren s trofinetide successful in proof of concept Phase 2 clinical trial in Fragile X syndrome

Neuren s trofinetide successful in proof of concept Phase 2 clinical trial in Fragile X syndrome Neuren (NEU) - ASX Announcement 7 December 2015 Neuren s trofinetide successful in proof of concept Phase 2 clinical trial in Fragile X syndrome Highlights: Positive top-line results provide a strong rationale

More information

The Treatment of Rett Syndrome with Trofinetide (NNZ-2566): Past, Present, Future. Daniel Glaze, MD Baylor College of Medicine

The Treatment of Rett Syndrome with Trofinetide (NNZ-2566): Past, Present, Future. Daniel Glaze, MD Baylor College of Medicine The Treatment of Rett Syndrome with Trofinetide (NNZ-2566): Past, Present, Future Daniel Glaze, MD Baylor College of Medicine Multicenter Trials of Trofinetide Past: Neu-2566-RETT-001 Phase 2 in Adolescents

More information

SCIRF Award #2016 I-03 PI: Azizul Haque, PhD Grant Title: Neuron-specific Enolase and SCI

SCIRF Award #2016 I-03 PI: Azizul Haque, PhD Grant Title: Neuron-specific Enolase and SCI SCIRF Award #2016 I-03 PI: Azizul Haque, PhD Grant Title: Neuron-specific Enolase and SCI 10-month Technical Progress Report Enolase is a multifunctional glycolytic enzyme involved in growth control, hypoxia,

More information

Targeting the p75 Receptor to Inhibit Degenerative Signaling and Tau Phosphorylation/Misfolding/ Missorting: Preclinical through Phase 1

Targeting the p75 Receptor to Inhibit Degenerative Signaling and Tau Phosphorylation/Misfolding/ Missorting: Preclinical through Phase 1 Targeting the p75 Receptor to Inhibit Degenerative Signaling and Tau Phosphorylation/Misfolding/ Missorting: Preclinical through Phase 1 ADC Directors Meeting, April 18 th 2015 Frank M. Longo, Stanford

More information

Mary ET Boyle, Ph. D. Department of Cognitive Science UCSD

Mary ET Boyle, Ph. D. Department of Cognitive Science UCSD ? Mary ET Boyle, Ph. D. Department of Cognitive Science UCSD Christian S Lobsiger & Don W Cleveland (2007) Nature Neuroscience 10, 1355-1360 Astrocytes: interlinked gatekeepers of glutamate astrocytes

More information

GFP/Iba1/GFAP. Brain. Liver. Kidney. Lung. Hoechst/Iba1/TLR9!

GFP/Iba1/GFAP. Brain. Liver. Kidney. Lung. Hoechst/Iba1/TLR9! Supplementary information a +KA Relative expression d! Tlr9 5!! 5! NSC Neuron Astrocyte Microglia! 5! Tlr7!!!! NSC Neuron Astrocyte! GFP/Sβ/! Iba/Hoechst Microglia e Hoechst/Iba/TLR9! GFP/Iba/GFAP f Brain

More information

Research progress on the use of estrogen receptor agonist for treatment of spinal cord injury

Research progress on the use of estrogen receptor agonist for treatment of spinal cord injury Research progress on the use of estrogen receptor agonist for treatment of spinal cord injury Swapan K. Ray, PhD Professor, Department of Pathology, Microbiology, and Immunology USC School of Medicine,

More information

The Opportunity: Parkinson s disease, RLS, ADHD, and disease modification YKP10461

The Opportunity: Parkinson s disease, RLS, ADHD, and disease modification YKP10461 The Opportunity: Parkinson s disease, RLS, ADHD, and disease modification YKP10461 1 TABLE OF CONTENTS Profile Summary Mechanism of Action Clinical Study Results Pharmacologic Profile Safety and Toxicity

More information

Shift 1, 8 July 2018, 09:30-13:00

Shift 1, 8 July 2018, 09:30-13:00 Shift 1, 8 July 2018, 09:30-13:00 CNS patterning A001-A014 Stem cells: basic biology and postnatal neurogenesis - part I Development of neural systems: Molecular and genetic characterisationa Epigenetic

More information

Investor Presentation. 2 June 2017

Investor Presentation. 2 June 2017 Investor Presentation 2 June 2017 1 Forward looking statements This presentation contains forward looking statements that involve risks and uncertainties. Although we believe that the expectations reflected

More information

B-cell. Astrocyte SCI SCI. T-cell

B-cell. Astrocyte SCI SCI. T-cell RF #2015 P-01 PI: Azizul Haque, PhD Grant Title: Targeting Enolase in Spinal Cord Injury 12-month Technical Progress Report Progress Report (First Six Months): Enolase is one of the most abundantly expressed

More information

Veronika Borbélyová, MSc., PhD.

Veronika Borbélyová, MSc., PhD. Veronika Borbélyová, MSc., PhD. borbelyova.veronika88@gmail.com History Eugen Bleuler autism (from the Greek words autos = self, ismus = orientation, status) the patient reduces the contact with the outside

More information

Hypothalamic TLR2 triggers sickness behavior via a microglia-neuronal axis

Hypothalamic TLR2 triggers sickness behavior via a microglia-neuronal axis Hypothalamic TLR triggers sickness behavior via a microglia-neuronal axis Sungho Jin, *, Jae Geun Kim,, *, Jeong Woo Park, Marco Koch,, Tamas L. Horvath and Byung Ju Lee Department of Biological Sciences,

More information

Supplementary Figure 1. Western blot of hippocampal lysates from WT and Adcy1 KO mice demonstrates the specificity of the ADCY1 antibody.

Supplementary Figure 1. Western blot of hippocampal lysates from WT and Adcy1 KO mice demonstrates the specificity of the ADCY1 antibody. ADCY1 13 kda β-actin 45 kda Supplementary Figure 1. Western blot of hippocampal lysates from and mice demonstrates the specificity of the ADCY1 antibody. a DHPG perk1/2 ERK1/2 Relative level min 1.6 *

More information

TREATING NEUROINFLAMMATION, TREATING DISEASE

TREATING NEUROINFLAMMATION, TREATING DISEASE TREATING NEUROINFLAMMATION, TREATING DISEASE NeuroTherapia Developing novel biopharmaceuticals for the treatment of neuroinflammatory disorders NOVEL STRATEGY FOR REDUCING NEUROINFLAMMATION SIGNIFICANT

More information

Potential Treatment and Current Research in Phelan-McDermid Syndrome. 11/16/2016 Frambu Center for Rare Disorders

Potential Treatment and Current Research in Phelan-McDermid Syndrome. 11/16/2016 Frambu Center for Rare Disorders Potential Treatment and Current Research in Phelan-McDermid Syndrome 11/16/2016 Frambu Center for Rare Disorders Genetics is Complicated! Deletion 22q13: Therapies Under Investigation Intranasal insulin

More information

Targeted Treatments for Au0sm: from Genes to Pharmacology

Targeted Treatments for Au0sm: from Genes to Pharmacology Targeted Treatments for Au0sm: from Genes to Pharmacology Paul Wang, MD Associate Clinical Professor of Pediatrics, Yale University School of Medicine Vice President for Clinical Development, Seaside Therapeu0cs,

More information

For personal use only

For personal use only Fr persnal use nly NNZ-2566 Prgram Presented at Internatinal Autism Cnference SYDNEY, Australia, 7 August 2012: Dr Michael Snape, Chief Scientific Officer f Autism Therapeutics Ltd, gave a presentatin

More information

Microglia preconditioning (priming) in central nervous system pathologies

Microglia preconditioning (priming) in central nervous system pathologies Microglia preconditioning (priming) in central nervous system pathologies Florence Perrin florence.perrin@umontpellier.fr Montpellier, October 2018 1 Spanish anatomists Glia = glue in Greek Santiago Ramon

More information

In vivo effect of anti-inflammatory compounds on HIV-1 gp120 -mediated brain inflammation

In vivo effect of anti-inflammatory compounds on HIV-1 gp120 -mediated brain inflammation In vivo effect of anti-inflammatory compounds on HIV-1 gp120 -mediated brain inflammation Tamima Ashraf, PhD candidate Supervisor: Dr. Reina Bendayan University of Toronto, Leslie Dan Faculty of Pharmacy,

More information

Name/Institution: Fernanda Neutzling Kaufmann, PhD student at Post Graduate Program in Biochemistry, Federal University of Santa Catarina, Brazil

Name/Institution: Fernanda Neutzling Kaufmann, PhD student at Post Graduate Program in Biochemistry, Federal University of Santa Catarina, Brazil PROGRESS REPORT Committee for Aid and Education in Neurochemistry (CAEN) CATEGORY 1A: Visit by the applicant to another laboratory July, 2018 Name/Institution: Fernanda Neutzling Kaufmann, PhD student

More information

Pathways Toward Translational Research Programs for ASD. Helen Tager-Flusberg, Ph.D. Boston University NJ Governor s Council Conference April 9, 2014

Pathways Toward Translational Research Programs for ASD. Helen Tager-Flusberg, Ph.D. Boston University NJ Governor s Council Conference April 9, 2014 Pathways Toward Translational Research Programs for ASD Helen Tager-Flusberg, Ph.D. Boston University NJ Governor s Council Conference April 9, 2014 ASD Research History For several decades research on

More information

The Amazing Brain Webinar Series: Select Topics in Neuroscience and Child Development for the Clinician

The Amazing Brain Webinar Series: Select Topics in Neuroscience and Child Development for the Clinician The Amazing Brain Webinar Series: Select Topics in Neuroscience and Child Development for the Clinician Part VII Recent Advances in the Genetics of Autism Spectrum Disorders Abha R. Gupta, MD, PhD Jointly

More information

Chapter 11: Inherited Disorders of Human Memory Mental Retardation Syndromes. From Mechanisms of Memory, second edition By J. David Sweatt, Ph.D.

Chapter 11: Inherited Disorders of Human Memory Mental Retardation Syndromes. From Mechanisms of Memory, second edition By J. David Sweatt, Ph.D. Chapter 11: Inherited Disorders of Human Memory Mental Retardation Syndromes From Mechanisms of Memory, second edition By J. David Sweatt, Ph.D. Chapter 11: Mental Retardation Syndromes Table I: Mouse

More information

Topics in Pediatric Neurology: ASD and NF1. Hayley Drozd

Topics in Pediatric Neurology: ASD and NF1. Hayley Drozd Topics in Pediatric Neurology: ASD and NF1 Hayley Drozd Autism u Prevalence: 1/68 children u 4:1 male to female preference u 6:1 mild; 1.7:1 moderate-severe u Male: externalizing; Female: internalizing

More information

Subject Index. Bcl-2, apoptosis regulation Bone marrow, polymorphonuclear neutrophil release 24, 26

Subject Index. Bcl-2, apoptosis regulation Bone marrow, polymorphonuclear neutrophil release 24, 26 Subject Index A1, apoptosis regulation 217, 218 Adaptive immunity, polymorphonuclear neutrophil role 31 33 Angiogenesis cancer 178 endometrium remodeling 172 HIV Tat induction mechanism 176 inflammatory

More information

Assessing mouse behaviors: Modeling pediatric traumatic brain injury

Assessing mouse behaviors: Modeling pediatric traumatic brain injury Assessing mouse behaviors: Modeling pediatric traumatic brain injury Bridgette Semple Ph.D. Postdoctoral Fellow, Noble Laboratory Department of Neurological Surgery, UCSF Pediatric Traumatic Brain Injury

More information

Maternal Infection and Autism

Maternal Infection and Autism Maternal Infection and Autism Kristen Wierda Jackie Luu Nicole Chang Larysa Santavy October 17, 2017 Outline - What is autism? - Analyzing maternal infection - Model of Maternal Immune Activation (MIA)

More information

The Neurobiology of Psychiatric Disorders

The Neurobiology of Psychiatric Disorders The Neurobiology of Psychiatric Disorders Vikaas S. Sohal, MD PhD Department of Psychiatry Center for Integrative Neuroscience Sloan Swartz Center for Theoretical Neurobiology Overview 1. Classification

More information

Modulation of TRP channels by resolvins in mouse and human

Modulation of TRP channels by resolvins in mouse and human July 9, 2015, Ion Channel Retreat, Vancouver Ion Channel and Pain Targets Modulation of TRP channels by resolvins in mouse and human Ru-Rong Ji, PhD Pain Research Division Department of Anesthesiology

More information

Rapamycin suppresses astrocytic and microglial activation and reduces development of neuropathic pain after spinal cord injury in mice.

Rapamycin suppresses astrocytic and microglial activation and reduces development of neuropathic pain after spinal cord injury in mice. Rapamycin suppresses astrocytic and microglial activation and reduces development of neuropathic pain after spinal cord injury in mice. Satoshi Tateda, MD, Haruo Kanno, MD, PhD, Hiroshi Ozawa, MD, PhD,

More information

Macrophages and Exosomes Employ Brain Inflammation for CNS Delivery of Therapeutics A. Kabanov

Macrophages and Exosomes Employ Brain Inflammation for CNS Delivery of Therapeutics A. Kabanov Macrophages and Exosomes Employ Brain Inflammation for CNS Delivery of Therapeutics A. Kabanov Targeting Brain Inflammation in Disease Biochemical studies of brains from individuals with many neurologic

More information

Neuren presents at the Rettsyndrome.org 2016 Research Symposium

Neuren presents at the Rettsyndrome.org 2016 Research Symposium Neuren (NEU) - ASX Announcement 24 June 2016 Neuren presents at the Rettsyndrome.org 2016 Research Symposium Melbourne, Australia, 24 June 2016: Neuren Pharmaceuticals (ASX: NEU) today announced that its

More information

Scientific Discoveries Allow Development of Targeted Therapeutics for Individuals with Autism Spectrum Disorders

Scientific Discoveries Allow Development of Targeted Therapeutics for Individuals with Autism Spectrum Disorders Scientific Discoveries Allow Development of Targeted Therapeutics for Individuals with Autism Spectrum Disorders Randall L. Carpenter, M.D. Co-Founder, President and CEO August 9, 2012 Research Supported

More information

CEO Address Larry Glass

CEO Address Larry Glass CEO Address Larry Glass Annual Shareholders Meeting of Neuren Pharmaceuticals Limited, 20 May 2013 Good afternoon and thank you for joining us here today. This is the beginning of my 10 th year with Neuren

More information

p53 and Apoptosis: Master Guardian and Executioner Part 2

p53 and Apoptosis: Master Guardian and Executioner Part 2 p53 and Apoptosis: Master Guardian and Executioner Part 2 p14arf in human cells is a antagonist of Mdm2. The expression of ARF causes a rapid increase in p53 levels, so what would you suggest?.. The enemy

More information

Supplemental Table 1. Primers used for RT-PCR analysis of inflammatory cytokines Gene Primer Sequence

Supplemental Table 1. Primers used for RT-PCR analysis of inflammatory cytokines Gene Primer Sequence Supplemental Table 1. Primers used for RT-PCR analysis of inflammatory cytokines Gene Primer Sequence IL-1α Forward primer 5 -CAAGATGGCCAAAGTTCGTGAC-3' Reverse primer 5 -GTCTCATGAAGTGAGCCATAGC-3 IL-1β

More information

Charlie Taylor, PhD CpTaylor Consulting Chelsea, MI, USA

Charlie Taylor, PhD CpTaylor Consulting Chelsea, MI, USA Contribution of Calcium Channel α 2 δ Binding Sites to the Pharmacology of Gabapentin and Pregabalin Charlie Taylor, PhD CpTaylor Consulting Chelsea, MI, USA Disclosure Information Charlie Taylor, PhD

More information

Synaptic plasticity. Activity-dependent changes in synaptic strength. Changes in innervation patterns. New synapses or deterioration of synapses.

Synaptic plasticity. Activity-dependent changes in synaptic strength. Changes in innervation patterns. New synapses or deterioration of synapses. Synaptic plasticity Activity-dependent changes in synaptic strength. Changes in innervation patterns. New synapses or deterioration of synapses. Repair/changes in the nervous system after damage. MRC Centre

More information

Circuit Changes in NDD

Circuit Changes in NDD The Refractory Brain: Designing Drugs to Treat Challenging Disorders of the Central Nervous System Disclosure Statement financial relationships to disclose Molly Huntsman, PhD FRAXA Research Foundation:

More information

How Synapses Integrate Information and Change

How Synapses Integrate Information and Change How Synapses Integrate Information and Change Rachel Stewart class of 2016 https://nba.uth.tmc.edu/neuroscience/s1/chapter06.html https://nba.uth.tmc.edu/neuroscience/s1/chapter07.html Chris Cohan, Ph.D.

More information

Supplementary Figure 1. Microglia do not show signs of classical immune activation following MD a-b. Images showing immunoreactivity for MHCII (a)

Supplementary Figure 1. Microglia do not show signs of classical immune activation following MD a-b. Images showing immunoreactivity for MHCII (a) 1 Supplementary Figure 1. Microglia do not show signs of classical immune activation following MD a-b. Images showing immunoreactivity for MHCII (a) and CD45 (b) in fixed sections of binocular visual cortex

More information

Title: Chapter 5 Recorded Lecture. Speaker: Amit Dhingra Created by: (remove if same as speaker) online.wsu.edu

Title: Chapter 5 Recorded Lecture. Speaker: Amit Dhingra Created by: (remove if same as speaker) online.wsu.edu Title: Chapter 5 Recorded Lecture Speaker: Title: What Anthony is the title Berger/Angela of this lecture? Williams Speaker: Amit Dhingra Created by: (remove if same as speaker) online.wsu.edu Chapter

More information

Is Intrinsic Hyperexcitability in CA3 the Culprit for Seizures in Rett Syndrome?

Is Intrinsic Hyperexcitability in CA3 the Culprit for Seizures in Rett Syndrome? Current Literature In Basic Science Is Intrinsic Hyperexcitability in CA3 the Culprit for Seizures in Rett Syndrome? Network Hyperexcitability in Hippocampal Slices From Mecp2 Mutant Mice Revealed by Voltage-Sensitive

More information

The Calpain / Calpastatin System in TBI and Chronic Neurodegeneration

The Calpain / Calpastatin System in TBI and Chronic Neurodegeneration The Calpain / Calpastatin System in TBI and Chronic Neurodegeneration Kathryn E. Saatman, Ph.D. Departments of Physiology and Neurosurgery Spinal Cord and Brain Injury Research Center Saatman lab: Dr.

More information

Supplemental Table.1 Published preclinical research studies of progesterone use in adult traumatic brain injury Author Model Dose i Outcome

Supplemental Table.1 Published preclinical research studies of progesterone use in adult traumatic brain injury Author Model Dose i Outcome Supplemental Table.1 Published preclinical research studies of progesterone use in adult traumatic brain injury Author Model Dose i Outcome Roof et al, 1992 (96) Roof et al, 1993 (15) Roof et al, 1996

More information

SUPPLEMENTARY INFORMATION

SUPPLEMENTARY INFORMATION Supplementary Figure 1. Behavioural effects of ketamine in non-stressed and stressed mice. Naive C57BL/6 adult male mice (n=10/group) were given a single dose of saline vehicle or ketamine (3.0 mg/kg,

More information

Chapter 7. Discussion and impact

Chapter 7. Discussion and impact Chapter 7 Discussion and impact 225 Affective pathology is a complex construct which encompasses a pathological disturbance in primary emotions, rapidly shifting from neutral to intense perception, associated

More information

Trauma Resuscitation: more than just blood products

Trauma Resuscitation: more than just blood products Trauma Resuscitation: more than just blood products Benjamin T. Houseman, MD, PhD Assistant Professor in Residence Department of Anesthesia University of California San Francisco Traumatic injury Leading

More information

Insulin-Leptin Interactions

Insulin-Leptin Interactions Insulin-Leptin Interactions Ahmed S., Al-Azzam N., Cao B. Karshaleva B., Sriram S., Vu K. If you understand a system, you can predict it. Agenda - Energy homeostasis Overview of leptin and insulin Signaling

More information

ECM1 controls T H 2 cell egress from lymph nodes through re-expression of S1P 1

ECM1 controls T H 2 cell egress from lymph nodes through re-expression of S1P 1 ZH, Li et al, page 1 ECM1 controls T H 2 cell egress from lymph nodes through re-expression of S1P 1 Zhenhu Li 1,4,Yuan Zhang 1,4, Zhiduo Liu 1, Xiaodong Wu 1, Yuhan Zheng 1, Zhiyun Tao 1, Kairui Mao 1,

More information

renoprotection therapy goals 208, 209

renoprotection therapy goals 208, 209 Subject Index Aldosterone, plasminogen activator inhibitor-1 induction 163, 164, 168 Aminopeptidases angiotensin II processing 64 66, 214 diabetic expression 214, 215 Angiotensin I intrarenal compartmentalization

More information

Part 11: Mechanisms of Learning

Part 11: Mechanisms of Learning Neurophysiology and Information: Theory of Brain Function Christopher Fiorillo BiS 527, Spring 2012 042 350 4326, fiorillo@kaist.ac.kr Part 11: Mechanisms of Learning Reading: Bear, Connors, and Paradiso,

More information

Inflammation in dementia

Inflammation in dementia Inflammation in dementia V. Hugh Perry University of Southampton DPUK April 2018 Inflammation in Alzheimer s disease: consequence or contributor? Amyloid plaque Neurofibrillary tangle Nissl & Alzheimer

More information

TBI: Translational Issues and Opportunities. Alan I Faden MD John Povlishock PhD

TBI: Translational Issues and Opportunities. Alan I Faden MD John Povlishock PhD TBI: Translational Issues and Opportunities Alan I Faden MD John Povlishock PhD State of the Science: Translational Issues and Opportunities Translational Issues: Failed Clinical Trials - Animal Modeling

More information

Synaptic plasticityhippocampus. Neur 8790 Topics in Neuroscience: Neuroplasticity. Outline. Synaptic plasticity hypothesis

Synaptic plasticityhippocampus. Neur 8790 Topics in Neuroscience: Neuroplasticity. Outline. Synaptic plasticity hypothesis Synaptic plasticityhippocampus Neur 8790 Topics in Neuroscience: Neuroplasticity Outline Synaptic plasticity hypothesis Long term potentiation in the hippocampus How it s measured What it looks like Mechanisms

More information

9.01 Introduction to Neuroscience Fall 2007

9.01 Introduction to Neuroscience Fall 2007 MIT OpenCourseWare http://ocw.mit.edu 9.01 Introduction to Neuroscience Fall 2007 For information about citing these materials or our Terms of Use, visit: http://ocw.mit.edu/terms. Declarative memory conscious,

More information

PART I. INTRODUCTION TO BRAIN DEVELOPMENT

PART I. INTRODUCTION TO BRAIN DEVELOPMENT NEURAL DEVELOPMENT AND BRAIN PLASTICITY A PRÉCIS TO UNDERSTANDING THE EFFECTS OF EARLY ADVERSITY Charles A. Nelson III, Ph.D. Children s Hospital Boston/Harvard Medical School Harvard Center on the Developing

More information

Subject Index. neuronal survival promotion by insulinlike growth factor-i , 162 regulatory proteins 148, 162

Subject Index. neuronal survival promotion by insulinlike growth factor-i , 162 regulatory proteins 148, 162 Subject Index Acid-labile subunit (ALS) evaluation 84 function 84 growth hormone activity marker 91 growth hormone insensitivity levels 102, 104 Alzheimer s disease, insulin-like growth factor-i neuroprotection

More information

Supplemental Figure 1. Western blot analysis indicated that MIF was detected in the fractions of

Supplemental Figure 1. Western blot analysis indicated that MIF was detected in the fractions of Supplemental Figure Legends Supplemental Figure 1. Western blot analysis indicated that was detected in the fractions of plasma membrane and cytosol but not in nuclear fraction isolated from Pkd1 null

More information

The Role of Brain Inflammation in Epileptogenesis in TSC. CONTRACTING ORGANIZATION: Washington University School of Medicine St Louis, M

The Role of Brain Inflammation in Epileptogenesis in TSC. CONTRACTING ORGANIZATION: Washington University School of Medicine St Louis, M AD Award Number: W81XWH-12-1-0190 TITLE: The Role of Brain Inflammation in Epileptogenesis in TSC PRINCIPAL INVESTIGATOR: Michael Wong CONTRACTING ORGANIZATION: Washington University School of Medicine

More information

Neurogenesis in Adult Central Nervous System: Death of a Dogma

Neurogenesis in Adult Central Nervous System: Death of a Dogma Aristotle University of Thessaloniki, Greece, Nov. 2007 Neurogenesis in Adult Central Nervous System: Death of a Dogma Anton B. Tonchev Division of Cell Biology, Varna University of Medicine, Bulgaria

More information

Involvement of TLR4/STAT3 signaling in the antimelanoma effects of atractylenolide II. Fu Xiuqiong

Involvement of TLR4/STAT3 signaling in the antimelanoma effects of atractylenolide II. Fu Xiuqiong Involvement of TLR4/STAT3 signaling in the antimelanoma effects of atractylenolide II Fu Xiuqiong Melanoma fact Skin cancers Skin cancer deaths 2.3% 75% Melanoma Non-melanoma skin cancers ----American

More information

Master Slide. From Model Systems to Clinical Trials in Phelan-McDermid Syndrome. Alexander Kolevzon, MD

Master Slide. From Model Systems to Clinical Trials in Phelan-McDermid Syndrome. Alexander Kolevzon, MD Master Slide From Model Systems to Clinical Trials in Phelan-McDermid Syndrome Alexander Kolevzon, MD Clinical Director, Seaver Autism Center Director, Child and Adolescent Psychiatry Mount Sinai Health

More information

The Role of the Immune System in Translating Early-Life Experience to Later-Life Brain and Behavior

The Role of the Immune System in Translating Early-Life Experience to Later-Life Brain and Behavior The Role of the Immune System in Translating Early-Life Experience to Later-Life Brain and Behavior STACI D. BILBO DEPARTMENT OF PSYCHOLOGY AND NEUROSCIENCE DUKE UNIVERSITY Thanks to! Dr. Mark Hutchinson

More information

The role of Neutrophil Gelatinase Associated Lipocalin in linking Depression and Heart Failure.

The role of Neutrophil Gelatinase Associated Lipocalin in linking Depression and Heart Failure. The role of Neutrophil Gelatinase Associated Lipocalin in linking Depression and Heart Failure. Leonie Gouweleeuw 1, Uli LM Eisel 1,2, Pieter JW Naude 1, Regien G. Schoemaker 1,3 1 : Department of Molecular

More information

Functional Development of Neuronal Networks in Culture -An in vitro Assay System of Developing Brain for Endocrine Disruptors

Functional Development of Neuronal Networks in Culture -An in vitro Assay System of Developing Brain for Endocrine Disruptors Functional Development of Neuronal Networks in Culture -An in vitro Assay System of Developing Brain for Endocrine Disruptors Masahiro Kawahara and Yoichiro Kuroda Tokyo Metropolitan Institute for Neuroscience

More information

The Effects of Chemotherapy on Cognitive Behavior and Neurogenesis in an Animal Model of Pre- and Post- Menopausal Females

The Effects of Chemotherapy on Cognitive Behavior and Neurogenesis in an Animal Model of Pre- and Post- Menopausal Females The Effects of Chemotherapy on Cognitive Behavior and Neurogenesis in an Animal Model of Pre- and Post- Menopausal Females Samantha Pavlock (Medical Student) Pradeep Bhide and Deirdre McCarthy (Faculty

More information

Top Peer Reviewed Journals Neuroscience & Behavior

Top Peer Reviewed Journals Neuroscience & Behavior Top Peer Reviewed Journals Neuroscience & Behavior Presented to Iowa State University Presented by Thomson Reuters Neuroscience & Behavior The subject discipline for Neuroscience & Behavior is made of

More information

IL-6 - a hypertrophic factor

IL-6 - a hypertrophic factor IL-6 - a hypertrophic factor 3 rd CIM PhD Course Copenhagen, April 30 th, 2009 Pompeu Fabra University Department of Experimental and Health Sciences Barcelona, Spain Myogenesis MRF: muscle regulatory

More information

AUTISM: What we know. What is next?

AUTISM: What we know. What is next? AUTISM:.? This document begins a conversation concerning what we know and what we need to learn about autism and related developmental disorders. It is intended to provide an outline of recent research

More information

Neuronal Plasticity, Learning and Memory. David Keays Institute of Molecular Pathology

Neuronal Plasticity, Learning and Memory. David Keays Institute of Molecular Pathology Neuronal Plasticity, Learning and Memory David Keays Institute of Molecular Pathology http://keayslab.org Structure 1. What is learning and memory? 2. Anatomical basis 3. Cellular basis 4. Molecular

More information

MeCP2 and psychostimulantinduced behavioral adaptations. Anne E. West, M.D., Ph.D. Department of Neurobiology Duke University Medical Center

MeCP2 and psychostimulantinduced behavioral adaptations. Anne E. West, M.D., Ph.D. Department of Neurobiology Duke University Medical Center MeCP2 and psychostimulantinduced behavioral adaptations Anne E. West, M.D., Ph.D. Department of Neurobiology Duke University Medical Center Psychostimulants and antidepressants slowly change behavior Psychostimulants

More information

Disruption of the astrocytic TNFR1-GDNF axis accelerates motor neuron degeneration and disease progression in amyotrophic lateral sclerosis

Disruption of the astrocytic TNFR1-GDNF axis accelerates motor neuron degeneration and disease progression in amyotrophic lateral sclerosis Disruption of the astrocytic TNFR1-GDNF axis accelerates motor neuron degeneration and disease progression in amyotrophic lateral sclerosis Daniela Rossi Laboratory of Research on Neurodegenerative Disorders

More information

How Synapses Integrate Information and Change

How Synapses Integrate Information and Change How Synapses Integrate Information and Change Rachel Stewart class of 2016 http://neuroscience.uth.tmc.edu/s1/chapter06.html http://neuroscience.uth.tmc.edu/s1/chapter07.html Chris Cohan, Ph.D. Dept. of

More information

Neuroprotective properties of GLP-1 - a brief overview. Michael Gejl Jensen, MD Dept. Of Pharmacology, AU

Neuroprotective properties of GLP-1 - a brief overview. Michael Gejl Jensen, MD Dept. Of Pharmacology, AU Neuroprotective properties of GLP-1 - a brief overview Michael Gejl Jensen, MD Dept. Of Pharmacology, AU mg@farm.au.dk Agenda Glucagon-like peptide (GLP-1) GLP-1 and neuronal activity GLP-1 in disease-specific

More information

3rd International Conference on Neurology & Therapeutics.

3rd International Conference on Neurology & Therapeutics. 3rd International Conference on Neurology & Therapeutics www.neuroimmunology.ca Multiple sclerosis is a devastating disease The first description of the disease was mentioned in 14th century In 1838 Dr.

More information

Chairman s Address Dr. Richard Treagus

Chairman s Address Dr. Richard Treagus Chairman s Address Dr. Richard Treagus Annual Shareholders Meeting Of Neuren Pharmaceuticals Limited, 30 April 2014 Good morning Ladies and Gentlemen. Welcome to our Annual Shareholders Meeting in Melbourne.

More information

What Cell Make Up the Brain and Spinal Cord

What Cell Make Up the Brain and Spinal Cord What Cell Make Up the Brain and Spinal Cord Jennifer LaVail, Ph.D. (http://anatomy.ucsf.edu/pages/lavaillab/index.html) What kinds of cells are these?" Neuron?" Epithelial cell?" Glial cell?" What makes

More information

Published online October 10, 2016

Published online October 10, 2016 Published online October 10, 2016 reviewed by Jim C. Eisenach, Wake Forest University; Ronald Lindsay, Zebra Biologics; Remi Quirion, McGill University; and Tony L. Yaksh, University of California, San

More information

Intracellular MHC class II molecules promote TLR-triggered innate. immune responses by maintaining Btk activation

Intracellular MHC class II molecules promote TLR-triggered innate. immune responses by maintaining Btk activation Intracellular MHC class II molecules promote TLR-triggered innate immune responses by maintaining Btk activation Xingguang Liu, Zhenzhen Zhan, Dong Li, Li Xu, Feng Ma, Peng Zhang, Hangping Yao and Xuetao

More information

9.01 Introduction to Neuroscience Fall 2007

9.01 Introduction to Neuroscience Fall 2007 MIT OpenCourseWare http://ocw.mit.edu 9.01 Introduction to Neuroscience Fall 2007 For information about citing these materials or our Terms of Use, visit: http://ocw.mit.edu/terms. Working memory short-term

More information

Fragile X Syndrome & Recent Advances in Behavioural Phenotype Research Jeremy Turk

Fragile X Syndrome & Recent Advances in Behavioural Phenotype Research Jeremy Turk Fragile X Syndrome & Recent Advances in Behavioural Phenotype Research Jeremy Turk Institute of Psychiatry Psychology & Neurosciences, King s College, University of London Child & Adolescent Mental Health

More information

Ionotropic glutamate receptors (iglurs)

Ionotropic glutamate receptors (iglurs) Ionotropic glutamate receptors (iglurs) GluA1 GluA2 GluA3 GluA4 GluN1 GluN2A GluN2B GluN2C GluN2D GluN3A GluN3B GluK1 GluK2 GluK3 GluK4 GluK5 The general architecture of receptor subunits Unique properties

More information

Ganaxolone as a Treatment for Drug-Resistant Epilepsy in Children

Ganaxolone as a Treatment for Drug-Resistant Epilepsy in Children Ganaxolone as a Treatment for Drug-Resistant Epilepsy in Children ANTIEPILEPTIC DRUG and DEVICE TRIALS XIII May 13-15, 2015 Turnberry Isle Miami Hotel Gail M. Farfel, PhD Chief Development & Regulatory

More information

Cognitive Enhancement Strategies. Florian Plattner, James A. Bibb

Cognitive Enhancement Strategies. Florian Plattner, James A. Bibb Cognitive Enhancement Strategies Florian Plattner, James A. Bibb A decline in memory and cognitive function is a natural aspect of aging. In addition, cognitive deficits are comorbid with many mental disorders

More information

Crosstalk between Adiponectin and IGF-IR in breast cancer. Prof. Young Jin Suh Department of Surgery The Catholic University of Korea

Crosstalk between Adiponectin and IGF-IR in breast cancer. Prof. Young Jin Suh Department of Surgery The Catholic University of Korea Crosstalk between Adiponectin and IGF-IR in breast cancer Prof. Young Jin Suh Department of Surgery The Catholic University of Korea Obesity Chronic, multifactorial disorder Hypertrophy and hyperplasia

More information

Fragile X targeted pharmacotherapy: lessons learned and future directions

Fragile X targeted pharmacotherapy: lessons learned and future directions Erickson et al. Journal of Neurodevelopmental Disorders (2017) 9:7 DOI 10.1186/s11689-017-9186-9 REVIEW Fragile X targeted pharmacotherapy: lessons learned and future directions Craig A. Erickson 1,2*,

More information

Programmed necrosis, not apoptosis, is a key mediator of cell loss and DAMP-mediated inflammation in dsrna-induced retinal degeneration

Programmed necrosis, not apoptosis, is a key mediator of cell loss and DAMP-mediated inflammation in dsrna-induced retinal degeneration Programmed necrosis, not apoptosis, is a key mediator of cell loss and DAMP-mediated inflammation in dsrna-induced retinal degeneration The Harvard community has made this article openly available. Please

More information

Supplementary Materials for

Supplementary Materials for www.sciencesignaling.org/cgi/content/full/7/308/ra4/dc1 Supplementary Materials for Antipsychotics Activate mtorc1-dependent Translation to Enhance Neuronal Morphological Complexity Heather Bowling, Guoan

More information

Embryonic MGE Cells as a Treatment for Epilepsy December 1, 2012

Embryonic MGE Cells as a Treatment for Epilepsy December 1, 2012 Embryonic MGE Cells as a Treatment for Epilepsy December 1, 2012 Scott C. Baraban, PhD University of California, San Francisco American Epilepsy Society Annual Meeting Disclosure Name of Commercial Interest

More information

Supplementary Figures for TSC1 controls macrophage polarization to prevent inflammatory disorder by Linnan Zhu et al

Supplementary Figures for TSC1 controls macrophage polarization to prevent inflammatory disorder by Linnan Zhu et al Supplementary Figures for TSC1 controls macrophage polarization to prevent inflammatory disorder by Linnan Zhu et al Suppl. Fig. 1 Tissue DN C Proteins kd TSC1-17 TSC 1 loxp bp -48-285 ctin PEMs Neutrophils

More information

How Nicotinic Signaling Shapes Neural Networks

How Nicotinic Signaling Shapes Neural Networks How Nicotinic Signaling Shapes Neural Networks Darwin K. Berg Division of Biological Sciences University of California, San Diego Nicotinic Cholinergic Signaling Uses the transmitter ACh to activate cation-selective

More information