Neuroprotective Attributes of Gut-derived Urolithins in Parkinson’s Disease

Nov 23, 2025Molecular neurobiology

Brain-protecting effects of gut-produced urolithins in Parkinson's disease

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Abstract

Urolithins, derived from dietary ellagitannins, may provide neuroprotective benefits relevant to Parkinson's disease.

Urolithins are produced from dietary compounds and may exert antioxidant, anti-inflammatory, and protective effects on nerve cells.
Gastrointestinal issues, such as imbalanced gut bacteria and increased intestinal permeability, are linked to the onset and worsening of Parkinson's disease.
Urolithins may help preserve dopamine-producing neurons and inhibit the aggregation of harmful proteins associated with Parkinson's.
These compounds could activate cellular pathways that enhance antioxidant defenses and reduce oxidative stress.
Urolithins are also associated with decreased neuroinflammation and improved mitochondrial function.
Mechanistic insights suggest that urolithins may play a role in promoting cellular processes that support the health of neurons.

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Urolithins, a class of gut microbiota-derived metabolites, are produced from dietary ellagitannins and ellagic acid. Their pleiotropic activities, including antioxidant, anti-inflammatory, and mitophagy-enhancing effects, position them as promising candidates for Parkinson's disease (PD), a disorder increasingly understood through the lens of gut-brain axis dysfunction. Mounting evidence implicates gastrointestinal disturbances, including dysbiosis, increased intestinal permeability, and aberrant microbial signaling, as early events that may initiate or exacerbate neuropathological cascades in PD. In this context, urolithins represent a unique class of neuromodulatory agents operating at the intersection of host-microbiota co-metabolism and neuroprotection. This review synthesizes mechanistic insights into urolithin biosynthesis and interindividual variability in bioavailability, followed by a critical appraisal of their efficacy in preclinical PD models. We outline their relevance across key pathogenic dimensions, including preservation of dopaminergic neurons, inhibition of pathological α-synuclein aggregation and propagation, suppression of oxidative stress via nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway activation and enhancement of endogenous antioxidant defenses, attenuation of neuroinflammation through downregulation of pro-inflammatory cytokines and glial reactivity, rescue of mitochondrial dysfunction, and promotion of autophagy-lysosomal pathways to mitigate proteostatic failure. By translating mechanistic insights into a coherent therapeutic framework, this review highlights the promise of urolithins as microbiota-derived interventions capable of modifying the course of PD.

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Neuroprotective Attributes of Gut-derived Urolithins in Parkinson’s Disease

Abstract

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