Abstract
AbstractNeurological disorders encompass a diverse range of conditions that affect individuals’ cognitive, emotional, and social functioning. Though these disorders are multifactorial, genetic factors play a significant role in the pathogenesis. Synaptic gene mutations or synaptic protein dysfunction are shown to be closely associated with neuropathology, suggesting the term synaptopathies. These synaptic abnormalities affect the proper brain physiology, release, regulation of neurotransmitters, disrupting neuronal communication and leading to the manifestation of these disorders. Although significant progress has been made, this area still remains uncharted as the outlaw around mental health and exceeds the research work that has been done till date. This study aims at understanding the critical role of synaptic compartment by conducting comprehensive analysis of existing synaptic gene mutations responsible for the development of three significant disorders in the Indian population: autism spectrum disorder (ASD), epilepsy and schizophrenia. Ourin silicoanalysis reveals, mutations in genesRPL10, GABRA1andDRD2corresponds to ASD, Epilepsy and Schizophrenia, respectively are predicted to be deleterious. Further, the proteins encoded by these mutated genes - Large ribosomal subunit protein uL16, Gamma-aminobutyric acid receptor subunit alpha-1 and D(2) dopamine receptor results in altered protein-protein interactions possibly resulting in disturbing different neuronal functions. Specifically, the disturbed interaction between D(2) dopamine receptor NCS1 might hamper the presynaptic functions such as neurotransmitter release. Together, our study helps to further understand the synaptic signalling in the context of the Indian population, which indeed potentiates the usage of model systems to identify novel therapeutic targets aiding to focus on developing personalised medications.
Publisher
Cold Spring Harbor Laboratory