Changes in TDP-43 expression in development, aging, and in the neurofilament light protein knockout mouse
2015 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 36, no 2, 1151-1159 p.Article in journal (Refereed) Published
The transactive response DNA-binding protein 43 (TDP-43) has been identified as a neurofilament light (NF-L) messenger RNA (mRNA)-binding protein. Abnormally increased levels of TDP-43 are detected in patients with amyotrophic lateral sclerosis and a downregulation of NF-L mRNA. However, links between NF-L and TDP-43 expressions are unclear. In this study, we investigated whether the deficiency of NF-L protein can result in alterations in TDP-43 localization or protein expression and whether this is altered with aging. There was a significant increase in TDP-43 protein levels in the cortex and lumbar spinal cord in 12-month-old NF-L knockout (NF-L KO) mice, compared with wild-type (WT) C57BL/6 mice. However, there was no difference in either the phosphorylation of TDP-43 between WT and NF-L KO mice or the abnormal mislocalization 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 aging than the levels of TDP-43 expression.
Place, publisher, year, edition, pages
2015. Vol. 36, no 2, 1151-1159 p.
Transactive response DNA-binding protein 43 (TDP-43), Neurofilament light (NF-L), Amyotrophic lateral sclerosis (ALS), Phosphorylated TDP-43
IdentifiersURN: urn:nbn:se:uu:diva-252731DOI: 10.1016/j.neurobiolaging.2014.10.001ISI: 000352454400061PubMedID: 25457553OAI: oai:DiVA.org:uu-252731DiVA: diva2:811429