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Summer Research Fellowship Programme of India's Science Academies

Development of a multi-scale model for the pathways related to synaptic plasticity leading to the Fragile X Syndrome

Sannidhya Sharmah

Dept. of Chemical Engg., IIT Guwahati, Guwahati, Assam, 781039

Upinder Singh Bhalla

Professor, Dept. of Neurobiology, National Centre for Biological Sciences, Bengaluru, Karnataka, 560065

Abstract

Fragile X Syndrome (FXS) is an inherited condition characterized by an X chromosome that is abnormally susceptible to damage, especially by folic acid deficiency. Affected individuals tend to have limited intellectual functions along with exhibition of an elongated face, large or protruding ears, flat feet, and low muscle tone. It has been understood that Fragile X Syndrome is caused by a defect in a single gene, FMR1, which shuts down and fails to make its normal but vital protein product, FMRP. In this project an attempt has been made to study the neural pathways that lead to the failure of the FMR1 gene and eventually to the FXS. Computational simulations are being used as they provide a comprehensive understanding of any system using step by step methods. The current project aims at developing a fully-functional simulation model of the various neural pathways that give rise to synaptic plasticity and observe how these pathways interact with each other as well as how they might lead to FXS. The simulation results will enable us to pinpoint, at least to some extent, which pathways contribute mostly to the disorder and hence, develop ways to modify those pathways as a potential cure for the disease. Moreover, the model would also serve the purpose of a well-documented resource for people who are researching the related domains in neurobiology and function as an available record-book/database of the neural reactions for those people. A comprehensive model containing pathways ranging from the mGluR pathway to the BDNF pathway has been constructed here using the MOOSE (Multi-Scale Object Oriented Simulation Environment) platform. All the simulation results have been compared with results available from literature as extensively as possible.

Keywords: mGluR, BDNF, Wnt, Glutamate, GSK3, arrestin-3

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