title: SYNGAP1: Mind the Gap.
abstract: A cardinal feature of early stages of human brain development centers on the sensory, cognitive, and emotional experiences that shape neuronal-circuit formation and refinement. Consequently, alterations in these processes account for many psychiatric and neurodevelopmental disorders. Neurodevelopment disorders affect 3-4% of the world population. The impact of these disorders presents a major challenge to clinicians, geneticists, and neuroscientists. Mutations that cause neurodevelopmental disorders are commonly found in genes encoding proteins that regulate synaptic function. Investigation of the underlying mechanisms using gain or loss of function approaches has revealed alterations in dendritic spine structure, function, and plasticity, consequently modulating the neuronal circuit formation and thereby raising the possibility of neurodevelopmental disorders resulting from synaptopathies. One such gene, SYNGAP1 (Synaptic Ras-GTPase-activating protein) has been shown to cause Intellectual Disability (ID) with comorbid Autism Spectrum Disorder (ASD) and epilepsy in children. SYNGAP1 is a negative regulator of Ras, Rap and of AMPA receptor trafficking to the postsynaptic membrane, thereby regulating not only synaptic plasticity, but also neuronal homeostasis. Recent studies on the neurophysiology of SYNGAP1, using Syngap1 mouse models, have provided deeper insights into how downstream signaling proteins and synaptic plasticity are regulated by SYNGAP1. This knowledge has led to a better understanding of the function of SYNGAP1 and suggests a potential target during critical period of development when the brain is more susceptible to therapeutic intervention.
authors.affiliation: Narayana Nethralaya Post-Graduate Institute of Ophthalmology, Narayana Nethralaya Foundation, Narayana Health City Bangalore, India.
authors.forename: Nallathambi
authors.initials: N
authors.lastname: Jeyabalan
authors.affiliation: Neuroscience Unit, Jawaharlal Nehru Centre for Advanced Scientific Research Bangalore, India.
authors.forename: James P
authors.initials: JP
authors.lastname: Clement
keywords: SYNGAP; autism spectrum disorders; intellectual disability; learning and memory; neurodevelopmental disorders; synaptic plasticity