Angiotensin Type-1 Receptor Inhibition Reduces NLRP3 Inflammasome Upregulation Induced by Aging and Neurodegeneration in the of Male Rodents and Primary Mesencephalic Cultures

Overview

Journal Antioxidants (Basel)

Date 2022 Feb 25

PMID 35204211

Authors

Aloia Quijano

Carmen Diaz-Ruiz

Andrea Lopez-Lopez

Begona Villar-Cheda

Ana Munoz

Ana I Rodriguez-Perez

Jose L Labandeira-Garcia

Affiliations

Soon will be listed here.

Abstract

The tissue renin-angiotensin system (RAS) has been shown to be involved in prooxidative and proinflammatory changes observed in aging and aging-related diseases such as dopaminergic degeneration in Parkinson's disease (PD). We studied the activation of the NLRP3 inflammasome in the with aging and early stages of dopaminergic degeneration in PD models and, particularly, if the brain RAS, via its prooxidative proinflammatory angiotensin II (AngII) type 1 (AT1) receptors, mediates the inflammasome activation. from aged rats and mice and 6-hydroxydopamine PD models showed upregulation in transcription of inflammasome-related components (NLRP3, pro-IL1β and pro-IL18) and IL1β and IL18 protein levels, which was inhibited by the AT1 receptor antagonist candesartan. The role of the AngII/AT1 axis in inflammasome activation was further confirmed in rats intraventricularly injected with AngII, and in primary mesencephalic cultures treated with 6-hydroxydopamine, which showed inflammasome activation that was blocked by candesartan. Observations in the of young and aged AT1 and AT2 knockout mice confirmed the major role of AT1 receptors in nigral inflammasome activation. In conclusion, the inflammasome is upregulated by aging and dopaminergic degeneration in the , possibly related with a decrease in dopamine levels, and it is mediated by the AngII/AT1 axis.

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