Endoplasmic reticulum proteostasis impairment in aging
Abstract
Perturbed neuronal proteostasis is a salient feature shared by both aging and protein misfolding disorders. The proteostasis network controls the health of the proteome by integrating pathways involved in protein synthesis, folding, trafficking, secretion, and their degradation. A reduction in the buffering capacity of the proteostasis network during aging may increase the risk to undergo neurodegeneration by enhancing the accumulation of misfolded proteins. As almost one‐third of the proteome is synthetized at the endoplasmic reticulum (ER), maintenance of its proper function is fundamental to sustain neuronal function. In fact, ER stress is a common feature of most neurodegenerative diseases. The unfolded protein response (UPR) operates as central player to maintain ER homeostasis or the induction of cell death of chronically damaged cells. Here, we discuss recent evidence placing ER stress as a driver of brain aging, and the emerging impact of neuronal UPR in controlling global proteostasis at the whole organismal level. Finally, we discuss possible therapeutic interventions to improve proteostasis and prevent pathological brain aging.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 23, 2017
- Source ID
- 10.1111/acel.12599
Entities
People
- Claudia Duran‐aniotz
- Claudio Hetz
- Felipe Cabral‐miranda
- Gabriela Martínez
- Juan P. Vivar
Organizations
- ALS Therapy Alliance
- Air Force Office of Scientific Research
- Buck Institute for Research on Aging
- CONICYT
- Federal University of Rio de Janeiro
- Harvard T.H. Chan School of Public Health
- Muscular Dystrophy Association
- National Fund for Scientific and Technological Development
- Office of Naval Research Global
- The Michael J. Fox Foundation