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- Title
Targeting protein aggregation for the treatment of degenerative diseases.
- Authors
Eisele, Yvonne S.; Monteiro, Cecilia; Fearns, Colleen; Encalada, Sandra E.; Wiseman, R. Luke; Powers, Evan T.; Kelly, Jeffery W.
- Abstract
The aggregation of specific proteins is hypothesized to underlie several degenerative diseases, which are collectively known as amyloid disorders. However, the mechanistic connection between the process of protein aggregation and tissue degeneration is not yet fully understood. Here, we review current and emerging strategies to ameliorate aggregation-associated degenerative disorders, with a focus on disease-modifying strategies that prevent the formation of and/or eliminate protein aggregates. Persuasive pharmacological and genetic evidence now supports protein aggregation as the cause of postmitotic tissue dysfunction or loss. However, a more detailed understanding of the factors that trigger and sustain aggregate formation and of the structure-activity relationships underlying proteotoxicity is needed to develop future disease-modifying therapies.
- Subjects
DEGENERATION (Pathology); TISSUES; STRUCTURE-activity relationships; PHARMACOLOGY; DRUG therapy; MEDICAL research; THERAPEUTICS; DISEASES
- Publication
Nature Reviews Drug Discovery, 2015, Vol 14, Issue 11, p759
- ISSN
1474-1776
- Publication type
journal article
- DOI
10.1038/nrd4593