Microbial Genetic Screens for Monitoring Protein Misfolding Associated with Neurodegeneration: Tools for Identifying Disease-Relevant Genes and for Screening Synthetic and Natural Compound Libraries for the Discovery of Potential Therapeutics

Author(s): Kalliopi Kostelidou, Ilias Matis, Georgios Skretas*

Journal Name: Current Pharmaceutical Design

Volume 24 , Issue 19 , 2018


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Abstract:

Neurodegenerative Diseases (ND) are a major threat to the aging population and the lack of a single preventive or disease-modifying agent only serves to increase their impact. In the past few years, protein misfolding and the subsequent formation of neurotoxic oligomeric/aggregated protein species have emerged as a unifying theme underlying the pathology of these complex diseases. Recently developed microbial genetic screens and selection systems for monitoring ND-associated protein misfolding have allowed the establishment of highthroughput assays for the identification of cellular factors and processes that are important mediators of NDassociated proteotoxicities. In addition, such systems have facilitated the discovery of synthetic and natural compounds with the ability to rescue the misfolding and the associated pathogenic effects of aggregation-prone proteins associated with NDs. This review outlines such available systems in bacteria and yeast, whose usage will likely accelerate the pre-clinical discovery process for effective drugs against a variety of NDs with high socioeconomic impact.

Keywords: Neurodegenerative diseases, protein misfolding, protein aggregation, microbial genetic screening, high-throughput, polyphenolic natural products.

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Article Details

VOLUME: 24
ISSUE: 19
Year: 2018
Published on: 23 September, 2018
Page: [2055 - 2075]
Pages: 21
DOI: 10.2174/1381612824666180515143752
Price: $65

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