Role of P2X7 Receptors in Immune Responses During Neurodegeneration

Author(s)

Oliveira-Giacomelli, Agatha ^[1] ; Petiz, Lyvia Lintzmaier ^[1] ; Andrejew, Roberta ^[1] ; Turrini, Natalia ^[1] ; Silva, Jean Bezerra ^[1] ; Sack, Ulrich ^[2] ; Ulrich, Henning ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Dept Biochem, Inst Chem, Sao Paulo - Brazil

^[2] Univ Leipzig, Med Fac, Inst Clin Immunol, Leipzig - Germany

• Document type: Review article
• Source: FRONTIERS IN CELLULAR NEUROSCIENCE; v. 15, MAY 26 2021.
• Web of Science Citations: 0

Abstract

P2X7 receptors are ion-gated channels activated by ATP. Under pathological conditions, the extensive release of ATP induces sustained P2X7 receptor activation, culminating in induction of proinflammatory pathways with inflammasome assembly and cytokine release. These inflammatory conditions, whether occurring peripherally or in the central nervous system (CNS), increase blood-brain-barrier (BBB) permeability. Besides its well-known involvement in neurodegeneration and neuroinflammation, the P2X7 receptor may induce BBB disruption and chemotaxis of peripheral immune cells to the CNS, resulting in brain parenchyma infiltration. For instance, despite common effects on cytokine release, P2X7 receptor signaling is also associated with metalloproteinase secretion and activation, as well as migration and differentiation of T lymphocytes, monocytes and dendritic cells. Here we highlight that peripheral immune cells mediate the pathogenesis of Multiple Sclerosis and Parkinson's and Alzheimer's disease, mainly through T lymphocyte, neutrophil and monocyte infiltration. We propose that P2X7 receptor activation contributes to neurodegenerative disease progression beyond its known effects on the CNS. This review discusses how P2X7 receptor activation mediates responses of peripheral immune cells within the inflamed CNS, as occurring in the aforementioned diseases. (AU)

• FAPESP's process: 18/08426-0 - Indole alkaloid sub products of Maqui (Aristotelia chilensis) processing as food additives to Alzheimer's Disease treatment
• Grantee: Alexander Henning Ulrich
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/24553-5 - The role of P2Y1 receptor in Parkinsons Disease
• Grantee: Roberta Andrejew Caetano
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/07366-4 - Purine and kinin receptors as targets of study and therapeutic interventions in neurological diseases
• Grantee: Alexander Henning Ulrich
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/26852-0 - Study of purinergic receptors antagonism in the inflammatory process and microglial cells activation using in vitro and in vivo models of Parkinsons Disease
• Grantee: Ágatha Oliveira Giacomelli
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/10725-6 - Evaluation of purinergic receptors in the comorbidity of bipolar disorder and Alzheimer's Disease
• Grantee: Natalia Turrini
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)