Healthcare and Medicine Reference
cross-sectional and longitudinal studies in clinical trials. Until now, the most
intriguing results are obtained from healthy centenarians, which show the dif-
ferences of these subjects from normal elderly donors. Fibroblast cultures from
healthy centenarians showed the existence of a functional proteasome in these
subjects and similar characteristics to the younger rather than the old control
donors (647). In the other studies, a decline in the proteasomal activity has
been shown in human tissue for muscle (208, 645) and lens (648). Recent
studies have demonstrated that proteasome inhibition may occur in a wide
array of neurodegenerative disorders, including ischemia-reperfusion injury
(649), AD (343, 650, 651), and Parkinson's disease (652). In addition to neu-
rodegenerative disorders, proteasome activity has been demonstrated to be
impaired during the aging of the central nervous system (CNS) (639, 653).
Some CNS regions, including the brain stem and cerebellum, show decreases
in proteasome activity only in extremely aged rodents (653). Numerous immu-
nohistochemical studies have provided the initial evidence for probable pro-
teasome inhibition in AD, Parkinson's disease, and Lewy body disease
(654-657). Similar results have recently been reported to occur in several in
vitro and in vivo models of spinocerebellar ataxia and Huntington's disease
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