Study on the effect of Stress conditions on Alzheimer’s disease using yeast Aβ42-MRF oligomerisation model

N, Aarthi (2016) Study on the effect of Stress conditions on Alzheimer’s disease using yeast Aβ42-MRF oligomerisation model. Masters thesis, Indian Institute of Technology Hyderabad.

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Abstract

Alzheimer's disease (AD) is a severe neurodegenerative disorder characterized by an extracellular deposition of amyloid plaques, and an intraneuronal accumulation of neurofibrillary tangles in the brain of affected individuals. A 42 amino acid long Aβ42 peptide generated by proteolytic processing of the APP protein is a major component of the amyloid plaques, in which it is mainly represented in the form of detergent-insoluble amyloid fibers. Previously, the Aβ42 fibers have been considered to be the major pathogenic agents of AD. Thus Small molecules that prevent the formation of Aβ42 aggregates that lead to the formation of large plaques had previously been of interest. Recently, this hypothesis has been challenged by findings suggesting that fibrillar aggregates may represent inert dead-end products of the Aβ42 aggregation pathway. Considerable evidence now suggests that the primary neurotoxic effects are associated with soluble SDS-stable assemblies of Aβ42, such as 56 kDa Aβ42 dodecamers, or even smaller, low-n (dimers, trimers, and tetramers) oligomers of Aβ42, which seem to appear during the early stages of Aβ42 assembly, and could give rise to larger oligomers. Thus, the focus of putative therapeutic interventions have shifted towards unravelling compounds that inhibit the earliest stages of Aβ42 oligomerization. In yet another finding, the frequency of [PSI +] induction, the prion of Sup35 (Yeast Translation Termination Factor) increased with stress. This stress related prion induction can be extrapolated to AD using Aβ42-MRF oligomerisation model that mimics [PSI +].

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IITH Creators:
IITH CreatorsORCiD
Item Type: Thesis (Masters)
Uncontrolled Keywords: Not available, TD626
Subjects: Others > Biotechnology
Divisions: Department of Biotechnology
Depositing User: Team Library
Date Deposited: 17 Aug 2016 11:26
Last Modified: 17 Aug 2016 11:26
URI: http://raiith.iith.ac.in/id/eprint/2654
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