The A(2A) adenosine receptor, a member of the P1 purinergic receptor family, plays a crucial role in the pathophysiology of different neurodegenerative illnesses, including Alzheimer's disease (AD). It regulates both neurons and glial cells, thus modulating synaptic transmission and neuroinflammation. AD is a complex, progressive neurological condition that is the leading cause of dementia in the world's old population (>65 years of age). Amyloid peptide-beta extracellular accumulation and neurofibrillary tangles constitute the principal etiologic tracts, resulting in apoptosis, brain shrinkage, and neuroinflammation. Interestingly, a growing body of evidence suggests a role of NLRP3 inflammasome as a target to treat neurodegenerative diseases. It represents a tripartite multiprotein complex including NLRP3, ASC, and procaspase-1. Its activation requires two steps that lead with IL-1 beta and IL-18 release through caspase-1 activation. NLRP3 inhibition provides neuroprotection, and in recent years adenosine, through the A(2A) receptor, has been reported to modulate NLRP3 functions to reduce organ damage. In this review, we describe the role of NLRP3 in AD pathogenesis, both alone and in connection to A(2A) receptor regulation, in order to highlight a novel approach to address treatment of AD.

A2A Adenosine Receptor: A Possible Therapeutic Target for Alzheimer's Disease by Regulating NLRP3 Inflammasome Activity?

Merighi, Stefania
Primo
;
Nigro, Manuela
Secondo
;
Travagli, Alessia;Pasquini, Silvia;Borea, Pier Andrea;Varani, Katia;Vincenzi, Fabrizio;Gessi, Stefania
Ultimo
2022

Abstract

The A(2A) adenosine receptor, a member of the P1 purinergic receptor family, plays a crucial role in the pathophysiology of different neurodegenerative illnesses, including Alzheimer's disease (AD). It regulates both neurons and glial cells, thus modulating synaptic transmission and neuroinflammation. AD is a complex, progressive neurological condition that is the leading cause of dementia in the world's old population (>65 years of age). Amyloid peptide-beta extracellular accumulation and neurofibrillary tangles constitute the principal etiologic tracts, resulting in apoptosis, brain shrinkage, and neuroinflammation. Interestingly, a growing body of evidence suggests a role of NLRP3 inflammasome as a target to treat neurodegenerative diseases. It represents a tripartite multiprotein complex including NLRP3, ASC, and procaspase-1. Its activation requires two steps that lead with IL-1 beta and IL-18 release through caspase-1 activation. NLRP3 inhibition provides neuroprotection, and in recent years adenosine, through the A(2A) receptor, has been reported to modulate NLRP3 functions to reduce organ damage. In this review, we describe the role of NLRP3 in AD pathogenesis, both alone and in connection to A(2A) receptor regulation, in order to highlight a novel approach to address treatment of AD.
Merighi, Stefania; Nigro, Manuela; Travagli, Alessia; Pasquini, Silvia; Borea, Pier Andrea; Varani, Katia; Vincenzi, Fabrizio; Gessi, Stefania
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2497749
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