Tau Abnormalities and the Potential Therapy in Alzheimer’s Disease

Article type: Review Article

Authors: Almansoub, Hasan A.M.M.^{a; b; c} | Tang, Hui^{a; b} | Wu, Ying^{a; b} | Wang, Ding-Qi^{a; b} | Mahaman, Yacoubou Abdoul Razak^{a; b} | Wei, Na^{d; e} | Almansob, Yusra A. M.^f | He, Wei^{g; *} | Liu, Dan^{b; h; *}

Affiliations: [a] Department of Pathophysiology, Key Lab of Neurological Disorder of Education Ministry, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China | [b] The Institute of Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, P.R. China | [c] Department of Biology, Faculty of Science – Marib, Sana’a University, Marib, Yemen | [d] Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China | [e] Department of Pathology, School of Basic Medicine, Zhengzhou University, Zhengzhou, P.R. China | [f] Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China | [g] Department of Orthopedics’, Hubei Hospital of Traditional Chinese Medicine, Wuhan, Hubei, P.R. China | [h] Department of Genetics, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China

Correspondence: [*] Correspondence to: Dan Liu, Department of Genetics, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Hangkong Road, Wuhan, 430030, P.R. China. Tel.: +86 2783692625; Fax: +86 2783692608; E-mail: liudan_echo@mail.hust.edu.cn. or He Wei, E-mail: lidaoziyuan@163.com.

Abstract: Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases that is characterized by progressive memory loss and two main pathological hallmarks, including the extracellular amyloid plaques and intracellular neurofibrillary tangles. The microtubule-related protein tau is involved in the pathogenesis of many neurological diseases commonly known as tauopathies and is found to be abnormally hyperphosphorylated in AD and accumulated in neurons. Besides hyperphosphorylation, tau also undergoes abnormal glycosylation, ubiquitination, glycation, and other posttranslational modifications. These abnormalities lead to the aberrant aggregation of tau in the synaptic loci in AD. In this review, we highlighted the most recent studies about how tau is abnormally regulated and how those abnormalities play important roles in the pathogenesis of AD.

Keywords: Aggregation, Alzheimer’s disease, hyperphosphorylation, post-translational modifications, tau

DOI: 10.3233/JAD-180868

Journal: Journal of Alzheimer's Disease, vol. 67, no. 1, pp. 13-33, 2019