Commentary: XBP-1 Is a Cell-Nonautonomous Regulator of Stress Resistance and Longevity

• Published in: Frontiers in aging neuroscience Vol. 8; p. 182
• Main Authors: Martínez, Gabriela, Duran-Aniotz, Claudia, Cabral-Miranda, Felipe, Hetz, Claudio
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 03.08.2016; Frontiers Media S.A
• Subjects: Activating transcription factor 4; Aging; Alzheimer's disease; Amino acids; Antioxidants; Apoptosis; Cell growth; Endoplasmic reticulum; Gene expression; Homeostasis; Infectious diseases; Life expectancy; Life span; Mammals; Metabolism; Movement disorders; Nervous system; Neurodegenerative diseases; Neuroscience; Parkinson's disease; Proteasomes; Proteins; Public health; Quality control; Risk factors; Sensors; Stem cells; Transcription factors; Chile; United States > US; unfolded protein response (UPR); proteostasis cell stress and aging; protein misfolding and disease; aging; cell-nonautonomous; protein misfolding disease; proteostasis deficiencies
• ISSN: 1663-4365; 1663-4365
• DOI: 10.3389/fnagi.2016.00182

Cell 153, 1435–1447. doi: 10.1016/j.cell.2013.05.042 The life expectancy in the world's population is increasing, highlighting the need of better understanding of the cellular and molecular pathways that drive the aging process. Because aging is the major risk factor to develop neurodegenerative conditions such as Alzheimer's and Parkinson's disease, the number of patients affected is constantly increasing, representing a major social and economic problem. [...]studies in simple model organisms indicate that the buffering capacity of the proteostasis network (PN) is reduced during aging (Douglas and Dillin, 2010; Mardones et al., 2015). The PN is formed by different interrelated sub-networks including mechanisms responsible for protein translation, folding, synthesis, protein quality control, trafficking, secretion, and degradation (ERAD, proteasome, autophagy). PERK phosphorylates eIF2α; inhibiting the translation of proteins into the ER, in addition to induce the expression of the transcription factor ATF4 regulating genes involved in the antioxidant response, amino acid metabolism and folding.