The Dual Role of Glutamatergic Neurotransmission in Alzheimer's Disease: From Pathophysiology to Pharmacotherapy.
AD
AMPA
EAAT1/2
NMDA
ageing
amyoid-β
glucose
glutamate
metabotropic receptors
tau
therapeutic targets
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:
09 Oct 2020
09 Oct 2020
Historique:
received:
13
08
2020
revised:
28
09
2020
accepted:
05
10
2020
entrez:
14
10
2020
pubmed:
15
10
2020
medline:
27
2
2021
Statut:
epublish
Résumé
Alzheimer's disease (AD) is an age-related dementia and neurodegenerative disorder, characterized by Aβ and tau protein deposition impairing learning, memory and suppressing synaptic plasticity of neurons. Increasing evidence suggests that there is a link between the glucose and glutamate alterations with age that down-regulates glucose utilization reducing glutamate levels in AD patients. Deviations in brain energy metabolism reinforce the development of AD by hampering glutamate levels in the brain. Glutamate is a nonessential amino acid and the major excitatory neurotransmitter synthesized from glucose. Alterations in cerebral glucose and glutamate levels precede the deposition of Aβ plaques. In the brain, over 40% of neuronal synapses are glutamatergic and disturbances in glutamatergic function have been implicated in pathophysiology of AD. Nevertheless, targeting the glutamatergic system seems to be a promising strategy to develop novel, improved therapeutics for AD. Here, we review data supporting the involvement of the glutamatergic system in AD pathophysiology as well as the efficacy of glutamatergic agents in this neurodegenerative disorder. We also discuss exciting new prospects for the development of improved therapeutics for this devastating disorder.
Identifiants
pubmed: 33050345
pii: ijms21207452
doi: 10.3390/ijms21207452
pmc: PMC7589203
pii:
doi:
Substances chimiques
Biomarkers
0
Receptors, Ionotropic Glutamate
0
Glutamic Acid
3KX376GY7L
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
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