NLRP3 inflammasome and glia maturation factor coordinately regulate neuroinflammation and neuronal loss in MPTP mouse model of Parkinson's disease.

NLRP3 inflammasome and glia maturation factor coordinately regulate neuroinflammation and neuronal loss in MPTP mouse model of Parkinson's disease. Int Immunopharmacol. 2020 Apr 04;83:106441 Authors: Javed H, Thangavel R, Selvakumar GP, Dubova I, Schwartz N, Ahmed ME, Zaheer S, Kempuraj D, Iyer S, Zaheer A, Khan MM Abstract Neuroinflammation plays an active role in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease (PD). Earlier studies from this laboratory showed that glia maturation factor (GMF), a proinflammatory mediator; is up-regulated in the brain in neurodegenerative diseases and that deficiency of GMF showed decreased production of IL-1β and improved behavioral abnormalities in mouse model of PD. However, the mechanisms linking GMF and dopaminergic neuronal death have not been completely explored. In the present study, we have investigated the expression of NLRP3 inflammasome and caspase-1 in the substantia nigra (SN) of human PD and non-PD brains by immunohistochemistry. Wild-type (WT) and GMF-/- (GMF knock-out) mice were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP) and the brains were isolated for neurochemical and morphological examinations. NLRP3 and caspase-1 positive cells were found significantly increased in PD when compared to non-PD control brains. Moreover, GMF co-localized with α-Synuclein within reactive astrocytes in the midbrain of PD. Mice treated with...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research