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A 2A Adenosine Receptor Antagonists in Neurodegenerative Diseases.

Authors :
Merighi S
Borea PA
Varani K
Vincenzi F
Jacobson KA
Gessi S
Source :
Current medicinal chemistry [Curr Med Chem] 2022; Vol. 29 (24), pp. 4138-4151.
Publication Year :
2022

Abstract

Background: Alzheimer's disease (AD) is the most common form of dementia worldwide, with approximately 6 million cases reported in America in 2020. The clinical signs of AD include cognitive dysfunction, apathy, anxiety and neuropsychiatric signs, and pathogenetic mechanisms that involve amyloid peptide-β extracellular accumulation and tau hyperphosphorylation. Unfortunately, current drugs to treat AD can provide only symptomatic relief but are not disease-modifying molecules able to revert AD progression. The endogenous modulator adenosine, through A <subscript>2A</subscript> receptor activation, plays a role in synaptic loss and neuroinflammation, which are crucial for cognitive impairment and memory damage.<br />Objective: In this review, recent advances covering A <subscript>2A</subscript> adenosine receptor antagonists will be extensively reviewed, providing a basis for the rational design of future A <subscript>2A</subscript> inhibitors.<br />Methods: Herein, the literature on A <subscript>2A</subscript> adenosine receptors and their role in synaptic plasticity and neuroinflammation, as well as the effects of A <subscript>2A</subscript> antagonism in animal models of AD and in humans, are reviewed. Furthermore, current chemical and structure-based strategies are presented.<br />Results: Caffeine, the most widely consumed natural product stimulant and an A <subscript>2A</subscript> antagonist, improves human memory. Similarly, synthetic A <subscript>2A</subscript> receptor antagonists, as described in this review, may provide a means to fight AD.<br />Conclusion: This review highlights the clinical potential of A <subscript>2A</subscript> adenosine receptor antagonists as a novel approach to treat patients with AD.<br /> (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Details

Language :
English
ISSN :
1875-533X
Volume :
29
Issue :
24
Database :
MEDLINE
Journal :
Current medicinal chemistry
Publication Type :
Academic Journal
Accession number :
34844537
Full Text :
https://doi.org/10.2174/0929867328666211129122550