Purinergic receptors in cognitive disturbances

• Published in: Neurobiology of disease Vol. 185; p. 106229
• Main Authors: Illes, Peter, Ulrich, Henning, Chen, Jiang-Fan, Tang, Yong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2023; Elsevier
• Subjects: Adenosine A1/A2A receptors; Cognitive disturbances; Neurogenerative diseases; Psychiatric disorders; Purinergic P2X/P2Y receptors; APP; KO mice; BBG; CNT; CNS; LTP; PSEN; ENT; HMGB1; MDD; LPS; Aβ; CA1; R; NLRP3; sAPP; Purinergic P2X/P2Y receptors; AD; IL; PKC; Poly I:C; IP3; Adenosine A1/A2A receptors; PD; Neurogenerative diseases; Cognitive disturbances; REM; HD; Psychiatric disorders; TLR4; GLT-1
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2023.106229

Purinergic receptors (Rs) of the ATP/ADP, UTP/UDP (P2X, P2Y) and adenosine (A1, A2A)-sensitive classes broadly interfere with cognitive processes both under quasi normal and disease conditions. During neurodegenerative illnesses, high concentrations of ATP are released from the damaged neuronal and non-neuronal cells of the brain; then, this ATP is enzymatically degraded to adenosine. Thus, the primary injury in neurodegenerative diseases appears to be caused by various protein aggregates on which a superimposed damage mediated by especially P2X7 and A2AR activation develops; this can be efficiently prevented by small molecular antagonists in animal models of the above diseases, or are mitigated in the respective knockout mice. Dementia is a leading symptom in Alzheimer's disease (AD), and accompanies Parkinson's disease (PD) and Huntington's disease (HD), especially in the advanced states of these illnesses. Animal experimentation suggests that P2X7 and A2ARs are also involved in a number of psychiatric diseases, such as major depressive disorder (MDD), obsessive compulsive behavior, and attention deficit hyperactivity disorder. In conclusion, small molecular antagonists of purinergic receptors are expected to supply us in the future with pharmaceuticals which are able to combat in a range of neurological/psychiatric diseases the accompanying cognitive deterioration.