Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

A CRMP4-dependent retrograde axon-to-soma death signal in amyotrophic lateral sclerosis

R. Maimon, L. Ankol, T. Gradus Pery, T. Altman, A. Ionescu, R. Weissova, M. Ostrovsky, E. Tank, G. Alexandra, N. Shelestovich, Y. Opatowsky, A. Dori, S. Barmada, M. Balastik, E. Perlson

. 2021 ; 40 (17) : e107586. [pub] 20210630

Jazyk angličtina Země Velká Británie

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc22003799

Grantová podpora
P30 AG053760 NIA NIH HHS - United States

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.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22003799
003      
CZ-PrNML
005      
20220127145842.0
007      
ta
008      
220113s2021 xxk f 000 0|eng||
009      
AR
024    7_
$a 10.15252/embj.2020107586 $2 doi
035    __
$a (PubMed)34190355
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxk
100    1_
$a Maimon, Roy $u Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
245    12
$a A CRMP4-dependent retrograde axon-to-soma death signal in amyotrophic lateral sclerosis / $c R. Maimon, L. Ankol, T. Gradus Pery, T. Altman, A. Ionescu, R. Weissova, M. Ostrovsky, E. Tank, G. Alexandra, N. Shelestovich, Y. Opatowsky, A. Dori, S. Barmada, M. Balastik, E. Perlson
520    9_
$a 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.
650    _2
$a amyotrofická laterální skleróza $x genetika $x metabolismus $7 D000690
650    _2
$a zvířata $7 D000818
650    12
$a axonální transport $7 D001370
650    _2
$a axony $x metabolismus $7 D001369
650    _2
$a buněčná smrt $7 D016923
650    _2
$a buněčné linie $7 D002460
650    _2
$a kultivované buňky $7 D002478
650    _2
$a dyneiny $x metabolismus $7 D004398
650    _2
$a myši $7 D051379
650    _2
$a myši inbrední C57BL $7 D008810
650    _2
$a motorické neurony $x metabolismus $x patologie $7 D009046
650    _2
$a proteiny nervové tkáně $x genetika $x metabolismus $7 D009419
650    _2
$a signální transdukce $7 D015398
650    _2
$a superoxiddismutasa 1 $x genetika $7 D000072105
655    _2
$a časopisecké články $7 D016428
655    _2
$a Research Support, N.I.H., Extramural $7 D052061
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Ankol, Lior $u Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel $u Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
700    1_
$a Gradus Pery, Tal $u Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
700    1_
$a Altman, Topaz $u Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
700    1_
$a Ionescu, Ariel $u Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
700    1_
$a Weissova, Romana $u Institue of Physiology of the Czech Academy of Sciences, Prague, Czech Republic $u Faculty of Science, Charles University, Prague, Czech Republic
700    1_
$a Ostrovsky, Michael $u Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
700    1_
$a Tank, Elizabeth $u Department of Neurology, University of Michigan, Ann Arbor, MI, USA
700    1_
$a Alexandra, Gayster $u Department of Pathology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
700    1_
$a Shelestovich, Natalia $u Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel $u Department of Pathology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
700    1_
$a Opatowsky, Yarden $u The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Israel
700    1_
$a Dori, Amir $u Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel $u Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel $u Department of Neurology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
700    1_
$a Barmada, Sami $u Department of Neurology, University of Michigan, Ann Arbor, MI, USA
700    1_
$a Balastik, Martin $u Institue of Physiology of the Czech Academy of Sciences, Prague, Czech Republic
700    1_
$a Perlson, Eran $u Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel $u Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
773    0_
$w MED00001509 $t The EMBO journal $x 1460-2075 $g Roč. 40, č. 17 (2021), s. e107586
856    41
$u https://pubmed.ncbi.nlm.nih.gov/34190355 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20220113 $b ABA008
991    __
$a 20220127145839 $b ABA008
999    __
$a ok $b bmc $g 1751304 $s 1154948
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2021 $b 40 $c 17 $d e107586 $e 20210630 $i 1460-2075 $m EMBO journal $n EMBO J $x MED00001509
GRA    __
$a P30 AG053760 $p NIA NIH HHS $2 United States
LZP    __
$a Pubmed-20220113

Najít záznam

Citační ukazatele

Možnosti archivace