文章基本信息

标题：Enhancing protein disaggregation restores proteasome activity in aged cells
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作者：Veronica Andersson ; Sarah Hanzén ; Beidong Liu 等
期刊名称：Aging
出版年度：2013
卷号：5
期号：11
页码：802-812
出版社：U.S.Department of Health & Human Service
摘要：The. activity. of. the. ubiquitin©\proteasome. system,. UPS,. declines. during. aging. in. several. multicellular. organisms.The. reason. behind. this. decline. remains. elusive.. Here,. using. yeast. as. a. model. system,. we. show. that. while. the. level. andpotential. capacity. of. the. 26S. proteasome. is. maintained. in. replicatively. aged. cells,. the. UPS. is.not.functioning. properly. invivo.. As. a. consequence. cytosolic. UPS. substrates,. such. as.¦¤ssCPY*. are. stabilized,. accumulate,. and. form. inclusions.. Byintegrating. a. pGPD©\HSP104. recombinant. gene. into. the. genome,. we. were. able. to. constitutively. elevate. proteindisaggregase. activity,. which. diminished. the. accumulation. of. protein. inclusions. during. aging.. Remarkably,. this. elevateddisaggregation. restored. degradation. of. a. 26S. proteasome. substrate. in. aged. cells. without. elevating. proteasome. levels,demonstrating. that. age©\associated. aggregation. obstructs. UPS. function.. The. data. supports. the. existence. of. a. negativefeedback.loop.that. accelerates. aging.by.exacerbating.proteostatic. decline.once.misfolded. and.aggregation©\prone.proteinsreach.a.critical.level