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- W4205655756 abstract "Neurodegenerative diseases (NDs) are characteristic with progression of neuron degeneration, resulting in dysfunction of cognition and mobility. Many neurodegenerative diseases are because of proteinopathies that results from unusual protein accumulations and aggregations. The aggregation of misfolded proteins like β-amyloid, α-synuclein, tau, and polyglutamates are hallmarked in Alzheimer's disease (AD), which are undruggable targets, and usually do not respond to conventional small-molecule agents. Therefore, developing novel technology and strategy for reducing the levels of protein aggregates would be critical for treatment of AD. Recently, the emerging proteolysis targeting chimeras (PRPTACs) technology has been significantly considered for artificial and selective degradation of aberrant target proteins. These engineered bifunctional molecules engage target proteins to be degraded by either the cellular degradation machinery in the ubiquitin-proteasome system (UPS) or via the autophagy-lysosome degradation pathway. Although the application of PROTACs technology is preferable than oligonucleotide and antibodies for treatment of NDs, many limitations such as their pharmacokinetic properties, tissue distribution and cell permeabilities, still need to be corrected. Herein, we review the recent advances in PROTACs technology with their limitation for pharmaceutical targeting of aberrant proteins involved in Alzheimer's diseases. We also review therapeutic potential of dysregulated signaling such as PI3K/AKT/mTOR axis for the management of AD." @default.
- W4205655756 created "2022-01-25" @default.
- W4205655756 creator A5005394879 @default.
- W4205655756 creator A5007270267 @default.
- W4205655756 creator A5009694924 @default.
- W4205655756 creator A5086354882 @default.
- W4205655756 date "2022-01-01" @default.
- W4205655756 modified "2023-10-10" @default.
- W4205655756 title "PROTAC technology for the treatment of Alzheimer’s disease: advances and perspectives" @default.
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