Modelling of human tauopathies in Drosophila for identification of some novel putative genetic modifiers
Neurodegenerative disease is a broad term that mainly refers to the conditions in which neurons in the brain are primarily affected. Neurons are the building blocks of the nervous system which normally don’t reproduce or replace themselves, so when they are damaged or die they cannot be regenerated which leads to neurodegeneration. Tauopathies, as the name suggests, involves the dysregulation of the tau protein. It includes various diseases like Alzheimer’s, Frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP), Pick’s disease etc. They are age related neurodegenerative diseases that are characterized by the presence of aggregates of abnormally phosphorylated tau protein. The understanding of the molecular mechanisms of Tau pathophysiology is still not clear. In the past decade, the fruit fly Drosophila melanogaster has emerged as an excellent model for neurodegenerative diseases. As a model of tauopathy it displays prominent features of the human disease such as it possesses 75% conserved disease causing genes, compromised lifespan, locomotor functions and age-dependent neurodegeneration detected by the presence of vacuolization. In this project tauopathies were modeled in Drosophila by using two types of disease lines, tauV337M and tauR406W, which were then crossed with some modifiers to analyze their effect on disease progression. Interestingly all of the three modifiers used i.e. a, b and c gave rescue in terms of improvement in the external eye structure with both the disease lines but the latter two were better than the former.
Keywords: Neurodegenerative disease, tau pathophysiology, tau protein.