Is There Justification to Treat Neurodegenerative Disorders by Repurposing Drugs? The Case of Alzheimer's Disease, Lithium, and Autophagy.
Alzheimer Disease
/ drug therapy
Animals
Apoptosis
/ drug effects
Autophagy
/ drug effects
Bipolar Disorder
/ drug therapy
Drug Repositioning
Glycogen Synthase Kinase 3
/ metabolism
Homeostasis
/ drug effects
Humans
Lithium
/ pharmacology
Neurodegenerative Diseases
/ drug therapy
Neuroprotective Agents
/ pharmacology
Oxidative Stress
/ drug effects
Phosphoric Monoester Hydrolases
/ metabolism
Alzheimer’s disease
lithium
neurodegenerative disorders
repurposing drugs
treatment
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
27 Dec 2020
27 Dec 2020
Historique:
received:
02
12
2020
revised:
16
12
2020
accepted:
23
12
2020
entrez:
30
12
2020
pubmed:
31
12
2020
medline:
1
4
2021
Statut:
epublish
Résumé
Lithium is the prototype mood-stabilizer used for acute and long-term treatment of bipolar disorder. Cumulated translational research of lithium indicated the drug's neuroprotective characteristics and, thereby, has raised the option of repurposing it as a drug for neurodegenerative diseases. Lithium's neuroprotective properties rely on its modulation of homeostatic mechanisms such as inflammation, mitochondrial function, oxidative stress, autophagy, and apoptosis. This myriad of intracellular responses are, possibly, consequences of the drug's inhibition of the enzymes inositol-monophosphatase (IMPase) and glycogen-synthase-kinase (GSK)-3. Here we review lithium's neurobiological properties as evidenced by its neurotrophic and neuroprotective properties, as well as translational studies in cells in culture, in animal models of Alzheimer's disease (AD) and in patients, discussing the rationale for the drug's use in the treatment of AD.
Identifiants
pubmed: 33375448
pii: ijms22010189
doi: 10.3390/ijms22010189
pmc: PMC7795249
pii:
doi:
Substances chimiques
Neuroprotective Agents
0
Lithium
9FN79X2M3F
Glycogen Synthase Kinase 3
EC 2.7.11.26
Phosphoric Monoester Hydrolases
EC 3.1.3.2
myo-inositol-1 (or 4)-monophosphatase
EC 3.1.3.25
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Israel Science Foundation
ID : 333/15
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