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- Title
Proteostasis deregulation as a driver of C9ORF72 pathogenesis.
- Authors
Torres, Paulina; Cabral‐Miranda, Felipe; Gonzalez‐Teuber, Vicente; Hetz, Claudio
- Abstract
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two related neurodegenerative disorders that display overlapping features. The hexanucleotide repeat expansion GGGGCC (G4C2) in C9ORF72 gene has been causally linked to both ALS and FTD emergence, thus opening a novel potential therapeutic target for disease intervention. The main driver of C9ORF72 pathology is the disruption of distinct cellular processes involved in the function of the proteostasis network. Here we discuss main findings relating to the induction of neurodegeneration by C9ORF72 mutation and proteostasis deregulation, highlighting the role of the endoplasmic reticulum stress, nuclear transport, and autophagy in the disease process. We further discuss possible points of intervention to target proteostasis mediators to treat C9ORF72‐linked ALS/FTD.
- Subjects
FRONTOTEMPORAL dementia; NEURODEGENERATION; PATHOGENESIS; LITERARY criticism; AMYOTROPHIC lateral sclerosis
- Publication
Journal of Neurochemistry, 2021, Vol 159, Issue 6, p941
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/jnc.15529