BMB Rep. 2016; 49(8): 405-413  
Tau mis-splicing in the pathogenesis of neurodegenerative disorders
Sun Ah Park1,*, Sang Il Ahn1 & Jean-Marc Gallo2
1Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Korea, 2Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 9NU, UK
Correspondence to: Tel: +82-32-621-5221; Fax: +82-32-621-5014; E-mail: sapark@schmc.ac.kr
Published online: August 31, 2016.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

Abstract
Tau proteins, which stabilize the structure and regulate the dynamics of microtubules, also play important roles in axonal transport and signal transduction. Tau proteins are missorted, aggregated, and found as tau inclusions under many pathological conditions associated with neurodegenerative disorders, which are collectively known as tauopathies. In the adult human brain, tau protein can be expressed in six isoforms due to alternative splicing. The aberrant splicing of tau pre-mRNA has been consistently identified in a variety of tauopathies but is not restricted to these types of disorders as it is also present in patients with non-tau proteinopathies and RNAopathies. Tau mis-splicing results in isoform-specific impairments in normal physiological function and enhanced recruitment of excessive tau isoforms into the pathological process. A variety of factors are involved in the complex set of mechanisms underlying tau mis-splicing, but variation in the cis-element, methylation of the MAPT gene, genetic polymorphisms, the quantity and activity of spliceosomal proteins, and the patency of other RNA-binding proteins, are related to aberrant splicing. Currently, there is a lack of appropriate therapeutic strategies aimed at correcting the tau mis-splicing process in patients with neurodegenerative disorders. Thus, a more comprehensive understanding of the relationship between tau mis-splicing and neurodegenerative disorders will aid in the development of efficient therapeutic strategies for patients with a tauopathy or other, related neurodegenerative disorders.
Keywords: Isoform, Mechanism, Splicing, Tau, Tauopathy


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