Title :
Tau post-translational modifications in wild-type and human
amyloid precursor protein transgenic mice
Abstract :
- The microtubule-associated protein tau has been implicated in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative disorders
- Reducing tau levels ameliorates AD-related synaptic, network, and behavioral abnormalities in transgenic mice expressing human amyloid precursor protein ( hAPP )
- We used mass spectrometry to characterize the post-translational modification of endogenous tau isolated from wild-type and hAPP mice
- We identified seven types of tau modifications at 63 sites in wild-type mice
- Wild-type and hAPP mice had similar modifications, supporting the hypothesis that neuronal dysfunction in hAPP mice is enabled by physiological forms of tau
- Our findings provide clear evidence for acetylation and ubiquitination of the same lysine residues ; some sites were also targeted by lysine methylation
- Our findings refute the hypothesis of extensive O-linked N-acetylglucosamine (O-GlcNAc) modification of endogenous tau
- The complex post-translational modification of physiological tau suggests that tau is regulated by diverse mechanisms
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