S, Kiruthika
(2015)
Studies on Yeast Model of Amyotrophic Lateral Sclerosis and Alzheimer’s Disease.
Masters thesis, Indian Institute of Technology Hyderabad.
Abstract
Amyotrophic lateral Sclerosis (ALS) is a fatal neurodegenerative disease which affects the motor neurons. TDP- 43 was identified as the pathogenic protein in ALS. The cause of the sporadic ALS is unknown but, there are some links with occupations involving heavy labour, exposure to heavy metals, or a history of traumatic injury. TDP- 43 has been expressed in yeast to act as a disease model for ALS. This model exhibits some of the pathological features associated with ALS in humans, like cytoplasmic aggregation of the protein and cytotoxicity. In this work, yeast model of ALS was studied using fluorescence microscopy and spot assay to check for toxic effect of TDP43-YFP expression on the growth of cells. When basal level of protein expression is maintained, diffused fluorescence is observed which implies the protein is in monomeric state. When the protein is over expressed, the TDP43-YFP fusion proteins tend to aggregate and form fluorescent foci. The TDP43-YFP when expressed in yeast forms toxic aggregates which hinders the growth of cells. Effect of zinc was also checked on the aggregation of TDP43- YFP. The data shows that zinc promotes the aggregation of TDP43- YFP in yeast.
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