論文 - 詳細
RRC ID | 50066 |
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著者 | Tang M, Ji C, Pallo S, Rahman I, Johnson GVW. |
タイトル | Nrf2 mediates the expression of BAG3 and autophagy cargo adaptor proteins and tau clearance in an age-dependent manner. |
ジャーナル | Neurobiol Aging |
Abstract |
During aging, decreased efficiency of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation and autophagic processes in the brain may be a contributing factor in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. Therefore, we analyzed the expression of Bcl-2-associated athanogene 3, a cochaperone that mediates autophagy, and the autophagy adaptors NBR1, NDP52, and sequestosome 1/p62 in the brains of 4-, 8-, and 12-month-old wild-type and Nrf2 knockout (-/-) mice. We also analyzed the levels of total tau and phospho-tau species. There were minimal differences in the expression of autophagy-related genes or tau species in 4-month-old animals; however, by 12 months, all of these autophagy-associated genes were expressed at significantly lower levels in the Nrf2 (-/-) mice. The decreases in the autophagy-associated genes were accompanied by significantly elevated levels of phospho-tau species in the 12-month-old Nrf2 (-/-) brains. These findings indicate that Nrf2 regulation of autophagy-related genes likely plays a greater role in mediating the clearance of tau as an organism ages. |
巻・号 | 63 |
ページ | 128-139 |
公開日 | 2018-3-1 |
DOI | 10.1016/j.neurobiolaging.2017.12.001 |
PII | S0197-4580(17)30395-0 |
PMID | 29304346 |
PMC | PMC5801049 |
MeSH | Adaptor Proteins, Signal Transducing / genetics* Adaptor Proteins, Signal Transducing / metabolism* Aging / genetics* Aging / metabolism* Aging / pathology Alzheimer Disease / etiology Alzheimer Disease / genetics Alzheimer Disease / pathology Animals Apoptosis Regulatory Proteins / genetics* Apoptosis Regulatory Proteins / metabolism* Autophagy / genetics* Autophagy / physiology* Autophagy-Related Proteins / genetics* Autophagy-Related Proteins / metabolism* Brain / metabolism* Brain / pathology* Gene Expression / genetics* Mice, Inbred C57BL Mice, Knockout NF-E2-Related Factor 2 / metabolism NF-E2-Related Factor 2 / physiology* Neurodegenerative Diseases / etiology Neurodegenerative Diseases / genetics Neurodegenerative Diseases / pathology tau Proteins / metabolism* |
IF | 4.347 |
引用数 | 16 |
リソース情報 | |
実験動物マウス | RBRC01390 |