Urolithin A promotes mitophagy and suppresses NLRP3 inflammasome activation in lipopolysaccharide-induced BV2 microglial cells and MPTP-induced Parkinson's disease model

Jan 22, 2022Neuropharmacology

Urolithin A supports mitochondrial cleanup and reduces inflammation in immune brain cells and a Parkinson's disease model

AI simplified

Gut-Brain Axis on OpenScience ↗PubMed ↗DOI ↗

Abstract

Treatment with Urolithin A (UA) reduced the loss of dopaminergic neurons in a mouse model of Parkinson's disease.

UA may ameliorate behavioral deficits and neuroinflammation associated with Parkinson's disease.
The compound promotes mitophagy, which is important for mitochondrial health.
UA appears to restore mitochondrial function in microglial cells exposed to inflammation.
It reduces activation of the NLRP3 inflammasome, a key player in inflammatory responses.
Disruption of microglial mitophagy may lessen the neuroprotective effects of UA.

AI simplified

Microglia-mediated neuroinflammation and mitochondrial dysfunction play critical role in the pathogenic process of Parkinson's disease (PD). Mitophagy plays central role in mitochondrial quality control. Hence, regulation of microglial activation through mitophagy could be a valuable strategy in controlling microglia-mediated neurodegeneration and neuroinflammation. Urolithin A (UA) is a natural compound produced by gut bacteria from ingested ellagitannins (ETs) and ellagic acid (EA). Several preclinical studies have reported the beneficial effects of UA on age-related conditions by increasing mitophagy and blunting excessive inflammatory responses. However, the specific role of UA in pathology of PD remains unknown. In this study, we showed that treatment with UA reduced the loss of dopaminergic neurons, ameliorated behavioral deficits and neuroinflammation in MPTP mouse model of PD. Further study revealed that UA promotes mitophagy, restores mitochondrial function and attenuate proinflammatory response in BV2 microglial cells exposed to LPS. Moreover, UA also reduced NLRP3 inflammasome activation both in vitro and in vivo. Importantly, disruption of microglial mitophagy with pharmacological or genetic approach partly blunted the neuroprotective effects of UA in MPTP mouse model of PD. Collectively, these results provide strong evidence that UA protects against dopaminergic neurodegeneration and neuroinflammation. The mechanism may be related with its inhibition of NLRP3 inflammasome activation via promoting mitophagy in microglia.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Urolithin A promotes mitophagy and suppresses NLRP3 inflammasome activation in lipopolysaccharide-induced BV2 microglial cells and MPTP-induced Parkinson's disease model

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the gut-brain axis brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the gut-brain axis brief