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A CRMP4-dependent retrograde axon-to-soma death signal in amyotrophic lateral sclerosis
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SYSNO ASEP 0545405 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název A CRMP4-dependent retrograde axon-to-soma death signal in amyotrophic lateral sclerosis Tvůrce(i) Maimon, R. (IL)
Ankol, L. (IL)
Pery, T. G. (IL)
Altman, T. (IL)
Ionescu, A. (IL)
Weissová, Romana (FGU-C) ORCID, RID, SAI
Ostrovsky, M. (IL)
Tank, E. (US)
Alexandra, G. (IL)
Shelestovich, N. (IL)
Opatowsky, Y. (IL)
Dori, A. (IL)
Barmada, S. (US)
Balaštík, Martin (FGU-C) RID, ORCID
Perlson, E. (IL)Číslo článku e107586 Zdroj.dok. EMBO Journal. - : Wiley - ISSN 0261-4189
Roč. 40, č. 17 (2021)Poč.str. 19 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova ALS ; axonal transport ; CRMP4 ; dynein ; retrograde signaling Vědní obor RIV FH - Neurologie, neurochirurgie, neurovědy Obor OECD Clinical neurology CEP NV18-04-00085 GA MZd - Ministerstvo zdravotnictví GA21-24571S GA ČR - Grantová agentura ČR Způsob publikování Open access Institucionální podpora FGU-C - RVO:67985823 UT WOS 000668140200001 EID SCOPUS 85108976518 DOI 10.15252/embj.2020107586 Anotace Amyotrophic lateral sclerosis (ALS) is a fatal non-cell-autonomous neurodegenerative disease characterized by the loss of motor neurons (MNs). Mutations in CRMP4 are associated with ALS in patients, and elevated levels of CRMP4 are suggested to affect MN health in the SOD1G93A-ALS mouse model. However, the mechanism by which CRMP4 mediates toxicity in ALS MNs is poorly understood. Here, by using tissue from human patients with sporadic ALS, MNs derived from C9orf72-mutant patients, and the SOD1G93A-ALS mouse model, we demonstrate that subcellular changes in CRMP4 levels promote MN loss in ALS. First, we show that while expression of CRMP4 protein is increased in cell bodies of ALS-affected MN, CRMP4 levels are decreased in the distal axons. Cellular mislocalization of CRMP4 is caused by increased interaction with the retrograde motor protein, dynein, which mediates CRMP4 transport from distal axons to the soma and thereby promotes MN loss. Blocking the CRMP4-dynein interaction reduces MN loss in human-derived MNs (C9orf72) and in ALS model mice. Thus, we demonstrate a novel CRMP4-dependent retrograde death signal that underlies MN loss in ALS. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2022 Elektronická adresa https://doi.org/10.15252/embj.2020107586
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