Autophagy, proteasomes, lipofuscin, and oxidative stress in the aging brain |
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Authors: | Keller Jeffrey N Dimayuga Edgardo Chen Qinghua Thorpe Jeffrey Gee Jillian Ding Qunxing |
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Institution: | a 203 Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536-0230, USA b Department of Anatomy and Neurobiology, 203 Sanders-Brown Center on Aging, University of Kentucky, 800 S. Limestone, Lexington, KY 40536-0230, USA |
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Abstract: | In order to successfully respond to stress all cells rely on the ability of the proteasomal and lysosomal proteolytic pathways to continually maintain protein turnover. Increasing evidence suggests that as part of normal aging there are age-related impairments in protein turnover by the proteasomal proteolytic pathway, and perturbations of the lysosomal proteolytic pathway. Furthermore, with numerous studies suggest an elevated level of a specialized form of lysosomal proteolysis (autophagy or macroautophagy) occurs during the aging of multiple cell types. Age-related alterations in proteolysis are believed to contribute to a wide variety of neuropathological manifestations including elevations in protein oxidation, protein aggregation, and cytotoxicity. Within the brain altered protein turnover is believed to contribute to elevations in multiple forms of protein aggregation ranging from tangle and Lewy body formation, to lipofuscin-ceroid accumulation. In this review we discuss and summarize evidence for proteolytic alterations occurring in the aging brain, the contribution of oxidative stress to disruption of protein turnover during normal aging, the evidence for cross-talk between the proteasome and lysosomal proteolytic pathways in the brain, and explore the contribution of altered proteolysis as a mediator of oxidative stress, neuropathology, and neurotoxicity in the aging brain. |
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Keywords: | Autophagy Brain Lipofuscin Lysosome Neuron Oxidative stress Proteasome Protein aggregation |
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