AI Article Synopsis
- SYNGAP1 is a gene that encodes a vital protein for synaptic function and development in the brain, specifically among excitatory neurons.
- Mutations in SYNGAP1 lead to a neurodevelopmental disorder known as Mental retardation-type 5 (MRD5), characterized by intellectual disability, motor issues, and epilepsy.
- The review focuses on the clinical impacts of SYNGAP1 mutations, their effects on brain development and function, and compares them to fragile X syndrome to identify potential therapeutic approaches.
Article Abstract
SYNGAP1 is a gene that encodes the cytosolic protein SYNGAP1 (SYNaptic GTPase Activating Protein), an essential component of the postsynaptic density at excitatory glutamatergic neurons. SYNGAP1 plays critical roles in synaptic development, structure, function, and plasticity. Mutations in SYNGAP1 result in a neurodevelopmental disorder termed Mental retardation-type 5 (MRD5, OMIM #612621) with a phenotype consisting of intellectual disability, motor impairments, and epilepsy, attesting to the importance of this protein for normal brain development. Here we review the clinical and pathophysiological aspects of SYNGAP1 mutations with a focus on their effect on synaptogenesis, neural circuit function, and cellular plasticity. We conclude by comparing the molecular pathogenesis of SYNGAP1 mutations with those of another neurodevelopmental disorder that affects dendritic function and cellular plasticity, fragile X syndrome. Insights into the molecular similarities and differences underlying these disorders could lead to rationale therapy development.
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| http://dx.doi.org/10.1016/j.ijdevneu.2019.08.003 | DOI Listing |
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SYNGAP1 is a major regulator of synaptic plasticity through its interaction with synaptic scaffold proteins and modulation of Ras and Rap GTPase signaling pathways. mutations in humans are often associated with intellectual disability, epilepsy, and autism spectrum disorder. heterozygous loss-of-function results in impaired LTP, premature maturation of dendritic spines, learning disabilities and seizures in mice.
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Article Synopsis
- Autism spectrum disorder (ASD) is a neurodevelopmental disorder marked by challenges in social interaction and communication, alongside repetitive behaviors.
- The incidence of ASD has notably risen globally over the past three decades, and its genetic underpinnings involve over 1000 genes, highlighting its complex nature.
- This review emphasizes the role of synaptic pathology in ASD, focusing on genetic variants that affect synaptic structure and function, suggesting that these genetic mutations may be key contributors to the disorder's development.
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