Computational Biology Approach for Therapeutic Intervention of Alexander Disease by Post Transcriptional Gene Silencing

Tammanna Ravee Sahrawat

Abstract


Alexander disease (AxD) primarily affects the white matter of the central nervous system (CNS). It is an astrogliopathy in which Astroglial cells involved in maintenance homeostasis and providing defence to the brain are affected. Therefore their dysfunction has been implicated in a number of neurological, neuropsychiatric and neurodegerative disorders. GFAP (Glial fibrillary acidic protein) is the major intermediate filament protein present in astrocytes whose heterozygous missense mutations have been reported to be a cause of AxD. In the absence of any effective therapeutic intervention of AxD, in the present study PTGS (Post transcriptional gene silencing) approach to knock down mutant gfap gene. Various mutations causing AxD were checked for their pathogenicity using various in silico tools and 13 mutations were shortlisted based on their pathogenicity and probability of occurrence. Thereafter siRNA were designed against the mutant genes to silence them and thereby preventing the accumulation of mutant gfap that causes the pathophysiology of AxD.

Keywords


Alexander disease GFAP Neurodegenrative disorder PTGS In-silico

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References


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