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Age‐related neurodegenerative diseases
Author(s) -
Duggan Michael,
Torkzaban Bahareh,
Ahooyi Taha Mohseni,
Khalili Kamel,
Gordon Jennifer
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29248
Subject(s) - progeria , context (archaeology) , protein aggregation , cytosol , neurodegeneration , reactive oxygen species , microbiology and biotechnology , biology , chemistry , neuroscience , medicine , biochemistry , disease , enzyme , paleontology , gene
Converging evidence indicates the dysregulation of unique cytosolic compartments called stress granules (SGs) might facilitate the accumulation of toxic protein aggregates that underlie many age‐related neurodegenerative pathologies (ANPs). SG dynamics are particularly susceptible to the cellular conditions that are commonly induced by aging, including the elevation in reactive oxygen species and increased concentration of aggregate‐prone proteins. In turn, the persistent formation of these compartments is hypothesized to serve as a seed for subsequent protein aggregation. Notably, the protein quality control (PQC) machinery responsible for inhibiting persistent SGs (e.g., Hsc70–BAG3) can become compromised with age, suggesting that the modulation of such PQC mechanisms could reliably inhibit pathological processes of ANPs. As exemplified in the context of accelerated aging syndromes (i.e., Hutchinson–Gilford progeria), PQC enhancement is emerging as a potential therapeutic strategy, indicating similar techniques might be applied to ANPs. Collectively, these recent findings advance our understanding of how the processes that might facilitate protein aggregation are particularly susceptible to aging conditions, and present investigators with an opportunity to develop novel targets for ANPs.