Tau tubulin kinases in proteinopathy. (22nd May 2019)

• Record Type: Journal Article
• Authors: Taylor, Laura M.; McMillan, Pamela J.; Kraemer, Brian C.; Liachko, Nicole F.
• Is Part Of: FEBS journal. Volume 286:Number 13(2019)
• Page Start: 2434
• Page End: 2446
• Publication Date: 2019-05-22
• Subjects: ALS -- Alzheimer's disease -- CBD -- FTLD -- phosphorylation -- Pick's disease -- PSP -- tau -- tauopathy -- TDP‐43 -- TTBK1 -- TTBK2; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.14866
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : A number of neurodegenerative diseases are characterized by deposition of abnormally phosphorylated tau or TDP‐43 in disease‐affected neurons. These diseases include Alzheimer's disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis. No disease‐modifying therapeutics is available to treat these disorders, and we have a limited understanding of the cellular and molecular factors integral to disease initiation or progression. Phosphorylated tau and TDP‐43 are important markers of pathology in dementia disorders and directly contribute to tau‐ and TDP‐43‐related neurotoxicity and neurodegeneration. Here, we review the scope of tau and TDP‐43 phosphorylation in neurodegenerative disease and discuss recent work demonstrating the kinases TTBK1 and TTBK2 phosphorylate both tau and TDP‐43, promoting neurodegeneration. Abstract : Neuronal deposition of abnormally phosphorylated tau or TDP‐43 is a hallmark of several neurodegenerative disorders. Activated tau tubulin kinases (TTBK1/2) phosphorylate tau and TDP‐43, generating pathological aggregation‐prone species. Phosphorylated tau and TDP‐43 drive neurodegeneration; therefore, blocking TTBK1/2 kinase activation may protect against both tauopathy and TDP‐43 proteinopathy. In this review, we summarize the role of tau and TDP‐43 phosphorylation in neurodegenerative disease and highlight the kinases TTBK1/2.