Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 11, 2022

Autism spectrum disorder (ASD) is a prevalent and complex neurodevelopmental which has strong genetic basis. Despite the rapidly rising incidence of autism, little known about its aetiology, risk factors, disease progression. There are currently neither validated biomarkers for diagnostic screening nor specific medication autism. Over last two decades, there have been remarkable advances in genetics, with hundreds genes identified as being associated high The convergence neuroscience methods becoming more widely recognized significance elucidating pathological mechanisms Efforts devoted to exploring behavioural functions, key potential treatments Here, we highlight this review, emerging evidence shows that signal transduction molecular events involved processes such transcription, translation, synaptic transmission, epigenetics immunoinflammatory responses. This involvement important implications discovery precise targets Moreover, review recent insights into clinical autism from molecular, cellular, neural circuit, neurobehavioural aspects. Finally, challenges future perspectives discussed regard novel strategies predicated on biological features

Language: Английский

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Impaired calcium signaling in astrocytes modulates autism spectrum disorder-like behaviors in mice

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: May 31, 2021

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder. The mechanisms underlying ASD are unclear. Astrocyte alterations noted in patients and animal models. However, whether astrocyte dysfunction causal or consequential to ASD-like phenotypes mice unresolved. Type 2 inositol 1,4,5-trisphosphate 6 receptors (IP3R2)-mediated Ca2+ release from intracellular stores results the activation of astrocytes. Mutations IP3R2 gene associated with ASD. Here, we show that both IP3R2-null mutant astrocyte-specific conditional knockout display behaviors, such as atypical social interaction repetitive behavior. Furthermore, astrocyte-derived ATP modulates behavior through P2X2 prefrontal cortex possibly GABAergic synaptic transmission. These findings identify potential molecular player pathophysiology

Language: Английский

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Autism Spectrum Disorder: Neurodevelopmental Risk Factors, Biological Mechanism, and Precision Therapy

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 1819 - 1819

Published: Jan. 17, 2023

Autism spectrum disorder (ASD) is a heterogeneous, behaviorally defined neurodevelopmental disorder. Over the past two decades, prevalence of autism disorders has progressively increased, however, no clear diagnostic markers and specifically targeted medications for have emerged. As result, neurobehavioral abnormalities, neurobiological alterations in ASD, development novel ASD pharmacological therapy necessitate multidisciplinary collaboration. In this review, we discuss multiple animal models to contribute disease mechanisms as well new studies from disciplines assess behavioral pathology ASD. addition, summarize highlight mechanistic advances regarding gene transcription, RNA non-coding translation, abnormal synaptic signaling pathways, epigenetic post-translational modifications, brain-gut axis, immune inflammation neural loop abnormalities provide theoretical basis next step precision therapy. Furthermore, review existing tactics limits present challenges opportunities translating knowledge into clinical practice.

Language: Английский

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GABA tone regulation and its cognitive functions in the brain

Nature reviews. Neuroscience, Journal Year: 2023, Volume and Issue: 24(9), P. 523 - 539

Published: July 26, 2023

Language: Английский

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Hippocampal astrocytes encode reward location

Nature, Journal Year: 2022, Volume and Issue: 609(7928), P. 772 - 778

Published: Aug. 31, 2022

Language: Английский

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