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Changes in TDP-43 expression in development, ageing and in the neurofilament light protein knockout mouse

Citation

Liu, Y and Atkinson, R and Fernandez-Martos, CM and Kirkcaldie, MTK and Cui, H and Vickers, JC and King, AE, Changes in TDP-43 expression in development, ageing and in the neurofilament light protein knockout mouse, Neurobiology of Aging: Experimental and Clinical Research, 36, (2) pp. 1151-1159. ISSN 0197-4580 (2014) [Refereed Article]

Copyright Statement

Copyright 2014 Elsevier

DOI: doi:10.1016/j.neurobiolaging.2014.10.001

Abstract

The transactive response DNA-binding protein 43 (TDP-43) has been identified as a neurofilament light (NF-L) mRNA binding protein. Abnormally increased levels of TDP-43 are detected in patients with amyotrophic lateral sclerosis as well as a downregulation of NF-L mRNA. However, links between NF-L and TDP-43 expression are unclear. In this study, we investigated whether the deficiency of NF-L protein can result in alterations in TDP-43 localisation or protein expression and whether this is altered with ageing. There was a significant increase in TDP-43 protein levels in the cortex and lumbar spinal cord in 12-month old NF-L knockout (KO) mice, compared to wild-type (WT) C57BL/6 mice. However, there was no difference in the phosphorylation of TDP-43 between WT and NF-L KO mice, nor abnormal mislocalisation of TDP-43 to the cytoplasm in NF-L KO animals. Our findings suggest that NF-L protein or mRNA may negatively affect the expression of TDP-43 in the central nervous system. However, altered phosphorylation of TDP-43 may be more highly associated with ageing than levels of TDP-43 expression.

Item Details

Item Type:Refereed Article
Keywords:transactive response DNA-binding protein 43 (TDP-43), neurofilament-light (NF-L), amyotrophic lateral sclerosis (ALS), phosphorylated TDP-43
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurology and Neuromuscular Diseases
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Liu, Y (Ms Yao Liu)
Author:Atkinson, R (Ms Rachel Atkinson)
Author:Fernandez-Martos, CM (Dr Carmen Fernandez-Martos)
Author:Kirkcaldie, MTK (Dr Matthew Kirkcaldie)
Author:Vickers, JC (Professor James Vickers)
Author:King, AE (Associate Professor Anna King)
ID Code:96098
Year Published:2014
Web of Science® Times Cited:2
Deposited By:Wicking Dementia Research and Education Centre
Deposited On:2014-10-20
Last Modified:2017-11-06
Downloads:0

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