Repurposing of Trimetazidine for amyotrophic lateral sclerosis: A study in SOD1
SOD1G93A mice
Trimetazidine
amyotrophic lateral sclerosis
hypermetabolism
mitochondria
neurodegeneration
Journal
British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
revised:
09
09
2021
received:
16
07
2021
accepted:
23
10
2021
pubmed:
17
11
2021
medline:
14
4
2022
entrez:
16
11
2021
Statut:
ppublish
Résumé
Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by the degeneration of upper and lower motor neurons, progressive wasting and paralysis of voluntary muscles and is currently incurable. Although considered to be a pure motor neuron disease, increasing evidence indicates that the sole protection of motor neurons by a single targeted drug is not sufficient to improve the pathological phenotype. We therefore evaluated the therapeutic potential of the multi-target drug used to treatment of coronary artery disease, trimetazidine, in SOD1 As a metabolic modulator, trimetazidine improves glucose metabolism. Furthermore, trimetazidine enhances mitochondrial metabolism and promotes nerve regeneration, exerting an anti-inflammatory and antioxidant effect. We orally treated SOD1 Trimetazidine administration delays motor function decline, improves muscle performance and metabolism, and significantly extends overall survival of SOD1 In SOD1
Sections du résumé
BACKGROUND AND PURPOSE
Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by the degeneration of upper and lower motor neurons, progressive wasting and paralysis of voluntary muscles and is currently incurable. Although considered to be a pure motor neuron disease, increasing evidence indicates that the sole protection of motor neurons by a single targeted drug is not sufficient to improve the pathological phenotype. We therefore evaluated the therapeutic potential of the multi-target drug used to treatment of coronary artery disease, trimetazidine, in SOD1
EXPERIMENTAL APPROACH
As a metabolic modulator, trimetazidine improves glucose metabolism. Furthermore, trimetazidine enhances mitochondrial metabolism and promotes nerve regeneration, exerting an anti-inflammatory and antioxidant effect. We orally treated SOD1
KEY RESULTS
Trimetazidine administration delays motor function decline, improves muscle performance and metabolism, and significantly extends overall survival of SOD1
CONCLUSION AND IMPLICATIONS
In SOD1
Identifiants
pubmed: 34783031
doi: 10.1111/bph.15738
pmc: PMC9305494
doi:
Substances chimiques
Superoxide Dismutase
EC 1.15.1.1
Superoxide Dismutase-1
EC 1.15.1.1
Trimetazidine
N9A0A0R9S8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1732-1752Informations de copyright
© 2021 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
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