MCC950 reduces autophagy and improves cognitive function by inhibiting NLRP3-dependent neuroinflammation in a rat model of Alzheimer's disease.

Brain Behav Immun

Laboratory for Stem Cell & Restorative Neurology, Department of Biotechnology, Era's Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow 226003, India; Department of Stem Cell Biology and Regenerative Medicine, Era's Lucknow Medical College & Hospital, Era University, Sarfarazganj, Lucknow 226003, India. Electronic address:

Published: February 2024

Alzheimer's disease (AD) is the seventh most common cause of mortality and one of the major causes of disability and vulnerability in the elderly. AD is characterized by gradual cognitive deterioration, the buildup of misfolded amyloid beta (Aβ) peptide, and the generation of neurofibrillary tangles. Despite enormous scientific progress, there is no effective cure for AD. Thus, exploring new treatment options to stop AD or at least slow down its progress is important. In this study, we investigated the potential therapeutic effects of MCC950 on NLRP3-mediated inflammasome-driven inflammation and autophagy in AD. Rats treated with streptozotocin (STZ) exhibited simultaneous activation of the NLRP3 inflammasome and autophagy, as confirmed by Western blot, immunofluorescence, and co-immunoprecipitation analyses. MCC950, a specific NLRP3 inhibitor, was intraperitoneally administered (50 mg/kg body weight) to rats with AD-like symptoms induced by intracerebroventricular STZ injections (3 mg/kg body weight). MCC950 effectively suppressed STZ-induced cognitive impairment and anxiety by inhibiting NLRP3-dependent neuroinflammation. Moreover, our findings indicate that MCC950 exerts neuroprotective effects by attenuating autophagy in neuronal cells. The inhibiting effects of MCC950 on inflammasome activation and autophagy were reproduced in vitro, provding further mechansistic insights into MCC950 therapeutic action. Our findings suggest that MCC950 impedes the progression of AD and may also improve cognitive function through the mitigation of autophagy and NLRP3 inflammasome inhibition.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbi.2023.11.031DOI Listing

Publication Analysis

Top Keywords

mcc950
8
cognitive function
8
inhibiting nlrp3-dependent
8
nlrp3-dependent neuroinflammation
8
alzheimer's disease
8
effects mcc950
8
nlrp3 inflammasome
8
body weight
8
autophagy
6
mcc950 reduces
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!