The Pathophysiology of Fragile X (and What It Teaches Us about Synapses)

Annual Review of Neuroscience, Год журнала: 2012, Номер 35(1), С. 417 - 443

Опубликована: Май 20, 2012

Fragile X is the most common known inherited cause of intellectual disability and autism, it typically results from transcriptional silencing FMR1 loss encoded protein, FMRP (fragile mental retardation protein). an mRNA-binding protein that functions at many synapses to inhibit local translation stimulated by metabotropic glutamate receptors (mGluRs) 1 5. Recent studies on biology signaling pathways downstream mGluR1/5 have yielded deeper insight into how synaptic synthesis plasticity are regulated experience. This new knowledge has also suggested ways altered function can be corrected in fragile X, human clinical trials based this information under way.

Язык: Английский

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mTOR complexes in neurodevelopmental and neuropsychiatric disorders

Nature Neuroscience, Год журнала: 2013, Номер 16(11), С. 1537 - 1543

Опубликована: Окт. 28, 2013

Язык: Английский

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Terminal Axon Branching Is Regulated by the LKB1-NUAK1 Kinase Pathway via Presynaptic Mitochondrial Capture

Cell, Год журнала: 2013, Номер 153(7), С. 1510 - 1525

Опубликована: Июнь 1, 2013

Язык: Английский

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Translational Control in Synaptic Plasticity and Cognitive Dysfunction

Annual Review of Neuroscience, Год журнала: 2014, Номер 37(1), С. 17 - 38

Опубликована: Июль 8, 2014

Activity-dependent changes in the strength of synaptic connections are fundamental to formation and maintenance memory. The mechanisms underlying persistent hippocampus, specifically long-term potentiation depression, depend on new protein synthesis. Such thought be orchestrated by engaging signaling pathways that regulate mRNA translation neurons. In this review, we discuss key regulatory govern translational control response activity populations targeted these pathways. critical contribution over synthesis proper cognitive function is underscored human disorders associated with either silencing or mutation genes encoding proteins directly translation. light clinical implications, also consider therapeutic potential targeting dysregulated treat dysfunction.

Язык: Английский

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Shared Synaptic Pathophysiology in Syndromic and Nonsyndromic Rodent Models of Autism

Science, Год журнала: 2012, Номер 338(6103), С. 128 - 132

Опубликована: Сен. 15, 2012

Reversing Autism in Mice comprises a heterogeneous group of neurodevelopmental disorders characterized by defects communication and social inter action. A nonsyndromic forms autism is associated with mutations the neuroligin genes, which encode postsynaptic adhesion molecules. Using reversible knockout approach, Baudouin et al. (p. 128 , published online 13 September) investigated vivo functions neuroligin-3 mouse cerebellum. Mutant mice showed major defect metabotropic glutamate receptor–dependent, long-term potentiation; disrupted heterosynaptic competition; ectopic synapse formation vivo. These synaptic could be rescued reactivation gene adult.

Язык: Английский

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A Synaptic Perspective of Fragile X Syndrome and Autism Spectrum Disorders

Neuron, Год журнала: 2019, Номер 101(6), С. 1070 - 1088

Опубликована: Март 1, 2019

Язык: Английский

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Genes, circuits, and precision therapies for autism and related neurodevelopmental disorders

Science, Год журнала: 2015, Номер 350(6263)

Опубликована: Окт. 16, 2015

Help for neurodevelopmental disorders When the brain does not develop normally, disabilities that ensue can affect a person life. Sahin and Sur review how emerging knowledge of molecular biology behind suite is shedding light on group as whole. The new offers tantalizing leads toward more effective therapies. Science , this issue p. 10.1126/science.aab3897

Язык: Английский

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GABAergic Signaling as Therapeutic Target for Autism Spectrum Disorders

Frontiers in Pediatrics, Год журнала: 2014, Номер 2

Опубликована: Июль 8, 2014

γ-Aminobutyric acid (GABA), the main inhibitory neurotransmitter in adult brain, early postnatal life exerts a depolarizing and excitatory action. This depends on accumulation of chloride inside cell via cation-chloride importer NKCC1, being expression exporter KCC2 very low at birth. The developmentally regulated results extrusion with age shift GABA from to hyperpolarizing direction. action leads intracellular calcium rise through voltage-dependent channels and/or N-methyl-d-aspartate receptors. GABA-mediated signals regulate variety developmental processes proliferation migration, differentiation, synapse maturation, neuronal wiring. Therefore, it is not surprising that some forms neuro-developmental disorders such as autism spectrum (ASDs) are associated alterations GABAergic signaling impairment excitatory/inhibitory balance selective circuits. In this review, we will discuss how changes GABAA-mediated neurotransmission affect several ASDs including Fragile X, Angelman, Rett syndromes. Then, describe various animal models dysfunctions, highlighting their behavioral deficits possibility rescue them by targeting components synapse. particular, cases, reverting polarity responses direction diuretic bumetanide, blocker may have beneficial effects ASDs, thus opening new therapeutic perspectives for treatment these devastating disorders.

Язык: Английский

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Emerging connections between cerebellar development, behaviour and complex brain disorders

Nature reviews. Neuroscience, Год журнала: 2019, Номер 20(5), С. 298 - 313

Опубликована: Март 28, 2019

Язык: Английский

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A computational tool (H-MAGMA) for improved prediction of brain-disorder risk genes by incorporating brain chromatin interaction profiles

Nature Neuroscience, Год журнала: 2020, Номер 23(4), С. 583 - 593

Опубликована: Март 9, 2020

Язык: Английский

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