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Degradation or Aggregation: the Ramifications of Post-translational Modifications on Tau
Seoyoung Park1, Jung Hoon Lee1, Min Jae Lee1,*
1Department of Biochemistry and Molecular Biology and 2Neuroscience Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea,
3Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea
Abstract
Tau protein is encoded in the microtubule-associated protein tau (MAPT) gene and contributes to the stability of microtubules in axons. Despite of its basic isoelectric point and high solubility, tau is often found in intraneuronal filamentous inclusions such as paired helical filaments (PHFs), which are the primary constituent of neurofibrillary tangles (NFTs). This pathological feature is the nosological entity termed “tauopathies” which notably include Alzheimer's disease (AD). A proteinaceous signature of all tauopathies is hyperphosphorylation of the accumulated tau, which has been extensively studied as a major pharmacological target for AD therapy. However, in addition to phosphorylation events, tau undergoes a number of diverse posttranslational modifications (PTMs) which appear to be controlled by complex crosstalk. It remains to be elucidated which of the PTMs or their combinations have pro-aggregation or anti-aggregation properties. In this review, we outline the consequences of and communications between several key PTMs of tau, such as acetylation, phosphorylation, and ubiquitination, focusing on their roles in aggregation and degradation. We place emphasis on the structure of tau protofilaments from the human AD brain, which may be good targets to modulate etiological PTMs which cause tau aggregation.
Abstract, Accepted Manuscript [Submitted on April 11, 2018, Accepted on April 11, 2018]
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