RRC ID 50066
Author Tang M, Ji C, Pallo S, Rahman I, Johnson GVW.
Title Nrf2 mediates the expression of BAG3 and autophagy cargo adaptor proteins and tau clearance in an age-dependent manner.
Journal 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.
Volume 63
Pages 128-139
Published 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
Times Cited 16
Mice RBRC01390