Z. Zhang et al., "Cleavage of tau by asparagine endopeptidase mediates the neurofibrillary pathology in Alzheimer's disease," Nature Medicine, 20:1254-62,2014. Tangles of truncated tau proteins squished inside brain cells are a hallmark of Alzheimer's disease (AD), though their precise origins are mysterious. Aging, the strongest risk factor for AD, is linked to a drop in neurons' pH, hinting that acidosis might influence tau fragmentation. In 2008, Keqiang Ye of Emory University and colleagues discovered that at a pH of 6.0, a lysosomal enzyme called asparagine endopeptidase (AEP) moved into the cytoplasm and cleaved brain proteins. This led them to explore whether AEP also acted on tau.
展开▼
