Track topics on Twitter Track topics that are important to you
Maintaining cellular proteostasis is essential for oligodendrocyte viability and function; however, its underlying mechanisms remain unexplored. The UPR, comprising three parallel branches IRE1, PERK, and ATF6α, is a major mechanism that maintains cellular proteostasis by facilitating protein folding, attenuating protein translation, and enhancing autophagy and ERAD. Here we reported that impaired UPR in oligodendrocytes via deletion of PERK and ATF6α did not affect developmental myelination, but caused late-onset mature oligodendrocyte dysfunction and death in young adult mice. The detrimental effects of the impaired UPR on mature oligodendrocytes were accompanied by autophagy impairment and intracellular PLP accumulation, and were rescued by PLP deletion. Data indicate that PLP is degraded by autophagy and that intracellular PLP accumulation is cytotoxic to oligodendrocytes. Thus, these findings imply that the UPR is required for maintaining cellular proteostasis and the viability and function of mature oligodendrocytes in adults by regulating autophagy of PLP.
This article was published in the following journal.
Name: JCI insight
Glioblastoma (GBM) continues to show a poor prognosis despite advances in diagnostic and therapeutic approaches. The discovery of reliable prognostic indicators may significantly improve treatment out...
Vascular smooth muscle cells (VSMC) are the main cellular component of vessel wall. The changes of VSMC functions including phenotypic transformation and apoptosis play a critical role in the pathogen...
Although typically upregulated upon cellular stress, autophagy can also be utilized under homeostatic conditions as a quality control mechanism or in response to developmental cues. Here, we report th...
To determine the effect of osteopontin (OPN) on autophagy and autophagy-apoptosis interactions after SAH.
Long noncoding RNA plasmacytoma variant translocation 1 (PVT1) has been identified to implicate in the progression of osteoarthritis (OA). However, the mechanism underlying PVT1 in OA development rema...
The long term goal is to identify the potential therapeutic targets for the treatment of obesity and its associated disorders by studying the driving factors of activation of brown adipose...
Little is known about autophagy during HIV infection. Recently, two different teams reported important dysfunctions of autophagy in HIV-infected patients despite sustained suppressive anti...
The molecular mechanisms involved in venous endothelial dysfunction are largely unknowns. Autophagy is an intracellular mechanism devoted to the removal of damaged cytoplasmic elements. Pr...
Aging is inevitable and is the primary risk factor for developing cardiovascular disease. The molecular mechanisms that drive vascular dysfunction in the context of aging are incompletely ...
Autophagy is recognized as a central mechanism for the regulation of aging. . Osteoporosis (OA) and Alzheimer's disease (AD) are two forms of pathological aging, sometimes entangled, inclu...
Genes whose loss of function or gain of function MUTATION leads to the death of the carrier prior to maturity. They may be essential genes (GENES, ESSENTIAL) required for viability, or genes which cause a block of function of an essential gene at a time when the essential gene function is required for viability.
Proteins and enzymes that function, often as components of MULTIPROTEIN COMPLEXES, to assemble AUTOPHAGOSOMES and carry out AUTOPHAGY.
The potential of the FETUS to survive outside the UTERUS after birth, natural or induced. Fetal viability depends largely on the FETAL ORGAN MATURITY, and environmental conditions.
Those genes found in an organism which are necessary for its viability and normal function.
An autophagy related protein that is similar to UBIQUITIN-ACTIVATING ENZYME E1. It functions in CYTOPLASM to VACUOLE transport (Cvt) and AUTOPHAGY by activating ATG12 PROTEIN for its conjugation with ATG5 PROTEIN, as well as the conjugation of ATG8 FAMILY PROTEINS with phosphatidylethanolamine for ATG8 association to Cvt vesicles and AUTOPHAGOSOME membranes. It is also required for the nitrogen starvation response in yeast, MITOPHAGY; and autophagic cell death induced by CASPASE 8 inhibition.
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...