TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis

Sreedharan, Jemeen, Leigh, Nigel and et al, (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science, 319 (5870). pp. 1668-72. ISSN 1095-9203

Full text not available from this repository.

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder characterized pathologically by ubiquitinated TAR DNA binding protein (TDP-43) inclusions. The function of TDP-43 in the nervous system is uncertain, and a mechanistic role in neurodegeneration remains speculative. We identified neighboring mutations in a highly conserved region of TARDBP in sporadic and familial ALS cases. TARDBPM337V segregated with disease within one kindred and a genome-wide scan confirmed that linkage was restricted to chromosome 1p36, which contains the TARDBP locus. Mutant forms of TDP-43 fragmented in vitro more readily than wild type and, in vivo, caused neural apoptosis and developmental delay in the chick embryo. Our evidence suggests a pathophysiological link between TDP-43 and ALS

Item Type: Article
Additional Information: Additional authors: Ian P. Blair, Vineeta B. Tripathi, Xun Hu, Caroline Vance, Boris Rogelj, Steven Ackerley, Jennifer C. Durnall, Kelly L. Williams, Emanuele Buratti, Francisco Baralle, Jacqueline de Belleroche, J. Douglas Mitchell, P., Ammar Al-Chalabi, Christopher C. Miller, Garth Nicholson and Christopher E. Shaw
Schools and Departments: Brighton and Sussex Medical School > Clinical and Experimental Medicine
Brighton and Sussex Medical School > Neuroscience
Subjects: R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry > RC0346 Neurology. Diseases of the nervous system Including speech disorders
Related URLs:
Depositing User: Patricia Butler
Date Deposited: 14 Nov 2012 17:43
Last Modified: 25 Sep 2017 13:58
URI: http://sro.sussex.ac.uk/id/eprint/42522
📧 Request an update