Hemizygous deletion of Tbk1 worsens neuromuscular junction pathology in TDP-43
Amyotrophic Lateral Sclerosis
/ genetics
Animals
DNA-Binding Proteins
/ genetics
Gene Deletion
Gliosis
/ genetics
Humans
Immunohistochemistry
Mice
Mice, Knockout
Mice, Transgenic
Motor Neurons
/ pathology
Movement Disorders
/ genetics
Muscle Denervation
Mutation
Neuromuscular Junction
/ pathology
Protein Serine-Threonine Kinases
/ genetics
Spinal Cord
/ pathology
Journal
Experimental neurology
ISSN: 1090-2430
Titre abrégé: Exp Neurol
Pays: United States
ID NLM: 0370712
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
15
04
2020
revised:
26
09
2020
accepted:
04
10
2020
pubmed:
11
10
2020
medline:
20
4
2021
entrez:
10
10
2020
Statut:
ppublish
Résumé
Mutations in the genes TARDBP (encoding the TDP-43 protein) and TBK1 can cause familial ALS. Neuronal cytoplasmatic accumulations of the misfolded, hyperphosphorylated RNA-binding protein TDP-43 are the pathological hallmark of most ALS cases and have been suggested to be a key aspect of ALS pathogenesis. Pharmacological induction of autophagy has been shown to reduce mutant TDP-43 aggregates and alleviate motor deficits in mice. TBK1 is exemplary for several other ALS genes that regulate autophagy. Consequently, we employed double mutant mice with both a heterozygous Tbk1 deletion and transgenic expression of human TDP-43
Identifiants
pubmed: 33038415
pii: S0014-4886(20)30327-7
doi: 10.1016/j.expneurol.2020.113496
pii:
doi:
Substances chimiques
DNA-Binding Proteins
0
TARDBP protein, human
0
Tbk1 protein, mouse
EC 2.7.1.-
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
113496Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.