X-Message-Number: 24919
Date: Mon, 25 Oct 2004 05:20:58 -0700 (PDT)
From: Doug Skrecky <>
Subject: autophagy and aging brain

Int J Biochem Cell Biol. 2004 Dec;36(12):2376-91.
Autophagy, proteasomes, lipofuscin, and oxidative stress in the aging brain.
 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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