CD82-TRPM7-Numb signaling mediates age-related cognitive impairment.
Alzheimer’s disease
CD82
Memory
Numb
TRPM7 α-kinase
Journal
GeroScience
ISSN: 2509-2723
Titre abrégé: Geroscience
Pays: Switzerland
ID NLM: 101686284
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
27
08
2019
accepted:
04
10
2019
pubmed:
24
2
2020
medline:
18
3
2021
entrez:
24
2
2020
Statut:
ppublish
Résumé
Aging is a crucial cause of cognitive decline and a major risk factor for Alzheimer's disease (AD); however, AD's underlying molecular mechanisms remain unclear. Recently, tetraspanins have emerged as important modulators of synaptic function and memory. We demonstrate that the level of tetraspanin CD82 is upregulated in the brains of AD patients and middle-aged mice. In young adult mice, injection of AAV-CD82 to the hippocampus induced AD-like cognitive deficits and impairments in neuronal spine density. CD82 overexpression increased TRPM7 α-kinase cleavage via caspase-3 activation and induced Numb phosphorylation at Thr346 and Ser348 residues. CD82 overexpression promoted beta-amyloid peptide (Aβ) secretion which could be reversed by Numb T346S348 mutants. Importantly, hippocampus-related memory functions were improved in Cd82
Identifiants
pubmed: 32088828
doi: 10.1007/s11357-020-00166-4
pii: 10.1007/s11357-020-00166-4
pmc: PMC7205934
doi:
Substances chimiques
Amyloid beta-Peptides
0
CD82 protein, human
0
Kangai-1 Protein
0
Membrane Proteins
0
Nerve Tissue Proteins
0
Numb protein, mouse
0
TRPM Cation Channels
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
TRPM7 protein, human
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
595-611Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM125528
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG047879
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS056218
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG052363
Pays : United States
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