Glutamate: Molecular Mechanisms and Signaling Pathway in Alzheimer's Disease, a Potential Therapeutic Target.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, c1995-

Alzheimer Disease*/drug therapy ; Alzheimer Disease*/metabolism ; Signal Transduction*/drug effects ; Glutamic Acid*/metabolism ; Receptors, N-Methyl-D-Aspartate*/metabolism ; Receptors, N-Methyl-D-Aspartate*/antagonists & inhibitors; Humans ; Cholinesterase Inhibitors/therapeutic use ; Cholinesterase Inhibitors/pharmacology ; Animals ; Molecular Targeted Therapy

Gamma-glutamate is an important excitatory neurotransmitter in the central nervous system (CNS), which plays an important role in transmitting synapses, plasticity, and other brain activities. Nevertheless, alterations in the glutamatergic signaling pathway are now accepted as a central element in Alzheimer's disease (AD) pathophysiology. One of the most prevalent types of dementia in older adults is AD, a progressive neurodegenerative illness brought on by a persistent decline in cognitive function. Since AD has been shown to be multifactorial, a variety of pharmaceutical targets may be used to treat the condition. N-methyl-D-aspartic acid receptor (NMDAR) antagonists and acetylcholinesterase inhibitors (AChEIs) are two drug classes that the Food and Drug Administration has authorized for the treatment of AD. The AChEIs approved to treat AD are galantamine, donepezil, and rivastigmine. However, memantine is the only non-competitive NMDAR antagonist that has been authorized for the treatment of AD. This review aims to outline the involvement of glutamate (GLU) at the molecular level and the signaling pathways that are associated with AD to demonstrate the drug target therapeutic potential of glutamate and its receptor. We will also consider the opinion of the leading authorities working in this area, the drawback of the existing therapeutic strategies, and the direction for the further investigation.

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Keywords: Alzheimer’s disease; NMDAR antagonist; acetylcholinesterase inhibitors; glutamate; neurotransmitter

3KX376GY7L (Glutamic Acid)
0 (Receptors, N-Methyl-D-Aspartate)
0 (Cholinesterase Inhibitors)

Date Created: 20241217 Date Completed: 20241217 Latest Revision: 20250104

20250114

PMC11643865

10.3390/molecules29235744

39683904