A current pharmacologic agent versus the promise of next generation therapeutics to ameliorate protein misfolding and/or aggregation diseases. (June 2016)

• Record Type: Journal Article
• Authors: Baranczak, Aleksandra; Kelly, Jeffery W
• Is Part Of: Current opinion in chemical biology. Volume 32(2016)
• Page Start: 10
• Page End: 21
• Publication Date: 2016-06
• Subjects: Bioorganic chemistry -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Clinical biochemistry -- Periodicals; Biochemistry -- Periodicals; Chimie bio-organique -- Périodiques; Biologie -- Périodiques; 572.05
• DOI: 10.1016/j.cbpa.2016.01.009
• Languages: English
• ISSNs: 1367-5931

Abstract

Highlights: Protein misfolding and misassembly leads to amyloid diseases and tissue degeneration. Genetic and aggregation insights led to a drug for the transthyretin amyloidoses. Tafamidis prevents the progression of the otherwise fatal transthyretin amyloidoses. An understanding of the cellular proteostasis networks is emerging. Proteostasis regulators should be useful for treating protein misfolding diseases. Abstract : The list of protein aggregation-associated degenerative diseases is long and growing, while the portfolio of disease-modifying strategies is very small. In this review and perspective, we assess what has worked to slow the progression of an aggregation-associated degenerative disease, covering the underlying mechanism of pharmacologic action and what we have learned about the etiology of the transthyretin amyloid diseases and likely amyloidoses in general. Next, we introduce emerging therapies that should apply more generally to protein misfolding and/or aggregation diseases, approaches that rely on adapting the protein homeostasis or proteostasis network for disease amelioration.