Author/Editor		Sreedharan, Jemeen; Blair, Ian P; Tripathi, Vineeta B; Hu, Xun; Vance, Caroline; Rogelj, Boris; Ackerley, Steven; Durnall, Jennifer C; Williams, Kelly L; Buratti, Emanuele
Title		TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis
Type		članek
Source		Science
Vol. and No.		Letnik 319, št. 5870
Publication year		2008
Volume		str. 1668-72
Language		eng
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.
Descriptors		ADULT AMINO ACID SEQUENCE AMYOTROPHIC LATERAL SCLEROSIS ANIMALS APOPTOSIS CHO CELLS CHICK EMBRYO CHROMOSOMES, HUMAN, PAIR 1 CRICETULUS DNA-BINDING PROTEINS MICROSATELLITE REPEATS MOLECULAR SEQUENCE DATA NEURONS