Trends Neurosci 2021 Jun 5;44(6):424-440. Epub 2021 Apr 5.
Department of Stem Cell and Regenerative Biology, Department of Molecular and Cellular Biology, and Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address:
Transactive response DNA-binding protein 43 kDa (TDP-43), a multifunctional nucleic acid-binding protein, is a primary component of insoluble aggregates associated with several devastating nervous system disorders; mutations in TARDBP, its encoding gene, are a cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here, we review established and emerging roles of TDP-43 and consider how its dysfunction impinges on RNA homeostasis in the nervous system, thereby contributing to neural degeneration. Notably, improper splicing of the axonal growth-associated factor STMN2 has recently been connected to TDP-43 dysfunction, providing a mechanistic link between TDP-43 proteinopathies and neuropathy. Read More