Degradation or aggregation: the ramifications of post-translational modifications on tau

• Published in: BMB reports Vol. 51; no. 6; pp. 265 - 273
• Main Authors: Park, Seoyoung, Lee, Jung Hoon, Jeon, Jun Hyoung, Lee, Min Jae
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society for Biochemistry and Molecular Biology 01.06.2018; 생화학분자생물학회
• Subjects: Acetylation; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Animals; Axons - metabolism; Humans; Invited Mini Review; Microtubules - metabolism; Neurofibrillary Tangles - metabolism; Neurofibrillary Tangles - physiology; Phosphorylation; Protein Aggregates - physiology; Protein Processing, Post-Translational; Proteolysis; tau Proteins - genetics; tau Proteins - metabolism; Tauopathies - metabolism; Tauopathies - pathology; Ubiquitination; 화학
• ISSN: 1976-6696; 1976-670X
• DOI: 10.5483/bmbrep.2018.51.6.077

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. [BMB Reports 2018; 51(6): 265-273].