Polyglutamine (PolyQ) Diseases: Navigating the Landscape of Neurodegeneration.

Publisher: American Chemical Society Country of Publication: United States NLM ID: 101525337 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1948-7193 (Electronic) Linking ISSN: 19487193 NLM ISO Abbreviation: ACS Chem Neurosci Subsets: MEDLINE

Original Publication: Washington, D.C. : American Chemical Society

Peptides*/metabolism ; Neurodegenerative Diseases*/metabolism ; Neurodegenerative Diseases*/genetics; Humans ; Animals ; Huntington Disease/genetics ; Huntington Disease/metabolism

Polyglutamine (polyQ) diseases are a group of inherited neurodegenerative disorders caused by expanded cytosine-adenine-guanine (CAG) repeats encoding proteins with abnormally expanded polyglutamine tract. A total of nine polyQ disorders have been identified, including Huntington's disease, six spinocerebellar ataxias, dentatorubral pallidoluysian atrophy (DRPLA), and spinal and bulbar muscular atrophy (SBMA). The diseases of this class are each considered rare, yet polyQ diseases constitute the largest group of monogenic neurodegenerative disorders. While each subtype of polyQ diseases has its own causative gene, certain pathologic molecular attributes have been implicated in virtually all of the polyQ diseases, including protein aggregation, proteolytic cleavage, neuronal dysfunction, transcription dysregulation, autophagy impairment, and mitochondrial dysfunction. Although animal models of polyQ disease are available helping to understand their pathogenesis and access disease-modifying therapies, there is neither a cure nor prevention for these diseases, with only symptomatic treatments available. In this paper, we analyze data from the CAS Content Collection to summarize the research progress in the class of polyQ diseases. We examine the publication landscape in the area in effort to provide insights into current knowledge advances and developments. We review the most discussed concepts and assess the strategies to combat these diseases. Finally, we inspect clinical applications of products against polyQ diseases with their development pipelines. The objective of this review is to provide a broad overview of the evolving landscape of current knowledge regarding the class of polyQ diseases, to outline challenges, and evaluate growth opportunities to further efforts in combating the diseases.

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Keywords: CAG repeat; Huntington’s disease; dentatorubral pallidoluysian atrophy; pathogenesis; polyglutamine; protein aggregation; protein misfolding; spinal and bulbar muscular atrophy; spinocerebellar ataxia

26700-71-0 (polyglutamine)
0 (Peptides)

Date Created: 20240712 Date Completed: 20240807 Latest Revision: 20240811

20240812

PMC11311141

10.1021/acschemneuro.4c00184

38996083