Autophagy for the avoidance of neurodegeneration
TLDR
It is shown that inhibition of the UPR by knockout of XBP-1 causes a massive increase in autophagy, enhances clearance of superoxide dismutase 1 (SOD1) aggregates, and delays the development of amyotrophic lateral sclerosis.Abstract:
Cellular defense mechanisms, including the unfolded protein response (UPR) and autophagy, attempt to resolve toxic protein aggregates, which are common denominators of neurodegenerative diseases. In this issue of Genes & Development, Hetz and colleagues (pp. 2294-2306) surprisingly show that inhibition of the UPR by knockout of XBP-1 causes a massive increase in autophagy, enhances clearance of superoxide dismutase 1 (SOD1) aggregates, and delays the development of amyotrophic lateral sclerosis. These findings suggest the existence of a homeostatic-if not hormetic-balance between distinct cellular defense mechanisms.read more
Citations
More filters
Journal ArticleDOI
Molecular targets of oxidative stress.
TL;DR: A burgeoning understanding of the principal ROS targets will offer new possibilities for therapy of ROS related diseases.
Journal ArticleDOI
Can autophagy promote longevity
TL;DR: It is hypothesized that clearing cellular damage by autophagy is a common denominator of many lifespan-extending manipulations.
Journal ArticleDOI
Cellular stress responses, hormetic phytochemicals and vitagenes in aging and longevity.
Vittorio Calabrese,Carolin Cornelius,Albena T. Dinkova-Kostova,Albena T. Dinkova-Kostova,Ivo Iavicoli,Rosanna Di Paola,Aleardo Koverech,Salvatore Cuzzocrea,Enrico Rizzarelli,Edward J. Calabrese +9 more
TL;DR: How hormetic dose responses are mediated for endogenous cellular defense pathways including sirtuin, Nrfs and related pathways that integrate adaptive stress responses in the prevention of neurodegenerative diseases is described in mechanistic detail.
Journal ArticleDOI
Inducing Autophagy by Rapamycin Before, but Not After, the Formation of Plaques and Tangles Ameliorates Cognitive Deficits
TL;DR: It is shown that rapamycin, when given prophylactically to 2-month-old 3xTg-AD mice throughout their life, induces autophagy and significantly reduces plaques, tangles and cognitive deficits, and may represent a valid therapeutic strategy in AD when administered early in the disease progression.
Journal ArticleDOI
Stress-induced self-cannibalism: on the regulation of autophagy by endoplasmic reticulum stress
TL;DR: Current knowledge regarding how ER stress and the unfolded protein response (UPR) induce autophagy is reviewed, including description of the different autophagic-related genes which are regulated by the UPR.
References
More filters
Journal ArticleDOI
Autophagy in the Pathogenesis of Disease
TL;DR: This Review summarizes recent advances in understanding the physiological functions of autophagy and its possible roles in the causation and prevention of human diseases.
Journal ArticleDOI
Signal integration in the endoplasmic reticulum unfolded protein response
David Ron,Peter Walter +1 more
TL;DR: Together, at least three mechanistically distinct arms of the UPR regulate the expression of numerous genes that function within the secretory pathway but also affect broad aspects of cell fate and the metabolism of proteins, amino acids and lipids.
Journal ArticleDOI
TOR signaling in growth and metabolism.
TL;DR: The physiological consequences of mammalianTORC1 dysregulation suggest that inhibitors of mammalian TOR may be useful in the treatment of cancer, cardiovascular disease, autoimmunity, and metabolic disorders.
Journal ArticleDOI
Signal transduction by the JNK group of MAP kinases.
TL;DR: This review will focus on the JNK group of MAP kinases, which are characterized by the sequence TEY and the two stress-activatedMAP kinases: p38 with the sequence TGY, and the c-Jun NH2-terminal kinases (JNK) with the sequences TPY.
Journal ArticleDOI
Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
Taichi Hara,Kenji Nakamura,Makoto Matsui,Makoto Matsui,Makoto Matsui,Akitsugu Yamamoto,Yohko Nakahara,Rika Suzuki-Migishima,Minesuke Yokoyama,Kenji Mishima,Ichiro Saito,Hideyuki Okano,Noboru Mizushima +12 more
TL;DR: The results suggest that the continuous clearance of diffuse cytosolic proteins through basal autophagy is important for preventing the accumulation of abnormal proteins, which can disrupt neural function and ultimately lead to neurodegeneration.
Related Papers (5)
Autophagy in the Pathogenesis of Disease
Autophagy fights disease through cellular self-digestion
Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
Manuela Neumann,Deepak M. Sampathu,Linda K. Kwong,Adam C. Truax,Matthew Micsenyi,Thomas T. Chou,Jennifer Bruce,Theresa Schuck,Murray Grossman,Christopher M. Clark,Leo McCluskey,Bruce L. Miller,Eliezer Masliah,Ian R. A. Mackenzie,Howard Feldman,Wolfgang Feiden,Hans A. Kretzschmar,John Q. Trojanowski,Virginia M.-Y. Lee +18 more