Sunday, July 27, 2025

Urolithin a improves Parkinson's disease-associated cognitive impairment through modulation of neuroinflammation and neuroplasticity

 Your competent? doctor needs to do two things:

1. See if this would help cognitive impairment from stroke.

2. get human testing going because of your Parkinson's risk post stroke

Parkinson’s Disease May Have Link to Stroke March 2017   

I BET YOUR DOCTOR COMPLETELY FAILS AT BOTH!

Urolithin a improves Parkinson's disease-associated cognitive impairment through modulation of neuroinflammation and neuroplasticity


https://doi.org/10.1016/j.expneurol.2025.115395Get rights and content

Highlights

  • Urolithin A alleviates dopaminergic neurodegeneration and improves cognition in the sub-acute MPTP PD mouse model
  • Urolithin A alleviates neuronal injury and inflammatory responses within the hippocampal region in MPTP-treated mice
  • Urolithin A rescues synaptic damage and mitigates dendritic spine loss in the hippocampus of MPTP-treated mice
  • Urolithin A activates the AKT/CREB/BDNF signaling pathway in hippocampus
  • Urolithin A improves cognitive function in A53T α-synuclein transgenic PD mouse model.

Abstract

Cognitive impairment is one of the most common disabling non-motor manifestations of Parkinson's disease (PD), an age-onset condition for which there are no effective therapies available to date. Urolithin A (UA) is a natural compound produced by gut bacteria from ingested ellagitannins (ETs) and ellagic acid (EA). Our previous study showed that UA ameliorates motor deficits and dopaminergic neurodegeneration in experimental models of PD. However, its effect on PD non-motor symptoms has not been elucidated. This study aims to explore the effect of UA on cognitive impairment in MPTP-induced PD mouse model as well as in transgenic mice that overexpresses human A53T mutant α-synuclein (A53T mice). Treatment with UA reversed cognitive dysfunction as measured by Morris water maze, Y maze and novel object recognition tests in both PD models. Enhanced cognition was associated with decreased neuroinflammation in the hippocampus. Additionally, UA also reduced hippocampal neuronal dendritic spine loss and synaptic damage. Further mechanistic analyses revealed that the beneficial effects of UA on cognitive impairment appears to involve the activation of the highly protective AKT/CREB/BDNF signaling pathway. Collectively, these findings strongly suggest that UA mitigates cognitive deficits in both MPTP-induced PD mouse model and A53T mice by reducing neuroinflammation and sustaining neuroplasticity. This study provides the first evidence for a potential therapeutic effect of UA on cognitive impairment in vivo, and supports further assessment for the possible use of UA as a dietary supplement to prevent cognitive deficits in PD, and related neurodegenerative diseases.

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