Naslov
ALS and FTLD: two faces of TDP-43 proteinopathy

Autori
Liščić, Rajka M. ; Grinberg, T. Lea ; Zidar, Janez ; Gitcho, Michel A. ; Cairns, Nigel J.

Izvornik
European Journal of Neurology (1351-5101) 15 (2008), 8; 772-780

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, pregledni rad, znanstveni

Ključne riječi
frontotemporal lobar degeneration; TDP-43; ubiquitin; frontotemporal dementia; motor neuron disease; amyotrophic lateral sclerosis; granulin (GRN)

Sažetak
Major discoveries have been made in the recent past in the genetics, biochemistry and neuropathology of frontotemporal lobar degeneration (FTLD): Recently, TAR DNA-binding protein 43 (TDP-43) was identified as the major pathological protein of FTLD with ubiquitin-immunoreactive (ub-ir) inclusions (FTLD-U) with or without amyotrophic lateral sclerosis (ALS) and sporadic ALS. The majority of familial cases of FTLD-U are now known to have mutations in the granulin (GRN) gene. In the light of these important discoveries, we describe two kindreds with FTLD-U with GRN gene mutations: Hereditary Dysphasic Disinhibition Dementia Family 1 and 2 (HDDD1 and 2) characterized by changes in behavior and language deficits. Other FTLD-U entities with TDP-43 proteinopathy include: FTLD-U with valosin-containing protein (VCP) gene mutation and FTLD with ALS linked to chromosome 9p. In contrast, chromosome 3-linked dementia, FTLD-U with chromatin modifying protein 2B (CHMP2B) mutation, has ub-ir, TDP-43-negative inclusions. In summary, recent discoveries have generated new insights into the pathogenesis of a spectrum of disorders including: FTLD-U, FTLD-U with ALS and ALS. For the practicing neurologist, knowledge of these recent discoveries and a revised nosology of FTLD will contribute toward an accurate diagnosis, facilitate clinicopathological studies, and advance the quest for biomarkers and rational therapeutics.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

POVEZANOST RADA