A Prospective Repurposing of Dantrolene as a Multitarget Agent for Alzheimer's Disease.
Acetylcholinesterase
/ drug effects
Alzheimer Disease
/ drug therapy
Calcium
/ metabolism
Calcium Channel Blockers
/ chemistry
Carnitine
/ analogs & derivatives
Cell Line
Cholinesterase Inhibitors
/ chemistry
Dantrolene
/ chemistry
Drug Repositioning
Humans
Malignant Hyperthermia
/ drug therapy
Monoamine Oxidase
/ chemistry
Monoamine Oxidase Inhibitors
/ chemistry
Neuroprotective Agents
/ chemistry
Alzheimer’s disease
carnitine/acylcarnitine carrier
dantrolene
drug repurposing
multitarget activity
neuroprotection
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
25 Nov 2019
25 Nov 2019
Historique:
received:
23
10
2019
revised:
20
11
2019
accepted:
21
11
2019
entrez:
29
11
2019
pubmed:
30
11
2019
medline:
18
4
2020
Statut:
epublish
Résumé
The orphan drug dantrolene (DAN) is the only therapeutic treatment for malignant hyperthermia (MH), a pharmacogenetic pathology affecting 0.2 over 10,000 people in the EU. It acts by inhibiting ryanodine receptors, which are responsible for calcium recruitment in striatal muscles and brain. Because of its involvement in calcium homeostasis, DAN has been successfully investigated for its potential as neuroprotecting small molecule in several animal models of Alzheimer's disease (AD). Nevertheless, its effects at a molecular level, namely on putative targets involved in neurodegeneration, are still scarcely known. Herein, we present a prospective study on repurposing of DAN involving, besides the well-known calcium antagonism, inhibition of monoamine oxidase B and acetylcholinesterase, cytoprotection from oxidative insult, and activation of carnitine/acylcarnitine carrier, as concurring biological activities responsible for neuroprotection.
Identifiants
pubmed: 31775359
pii: molecules24234298
doi: 10.3390/molecules24234298
pmc: PMC6930524
pii:
doi:
Substances chimiques
Calcium Channel Blockers
0
Cholinesterase Inhibitors
0
Monoamine Oxidase Inhibitors
0
Neuroprotective Agents
0
acylcarnitine
0
Monoamine Oxidase
EC 1.4.3.4
Acetylcholinesterase
EC 3.1.1.7
Dantrolene
F64QU97QCR
Carnitine
S7UI8SM58A
Calcium
SY7Q814VUP
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : MIUR
ID : FFABR 2017
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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