Short-Chain Fatty Acids as a Therapeutic Strategy in Parkinson’s Disease: Implications for Neurodegeneration

📖 Top 20% JournalOct 22, 2025Cellular and molecular neurobiology

Using Short-Chain Fatty Acids to Treat Parkinson's Disease and Related Brain Cell Loss

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Abstract

Gut-derived (SCFAs) play a crucial role in maintaining neurological health.

Neurodegeneration leads to cognitive and motor skill deficits.
Parkinson's disease is characterized by dopaminergic neurodegeneration and an inflammatory brain environment.
Short-chain fatty acids are produced from dietary fiber fermentation and are important for intestinal and neural health.
SCFAs have anti-inflammatory effects and help maintain the integrity of the blood-brain barrier.
Butyrate, a type of SCFA, has neuroprotective capabilities, including enhancing mitochondrial function.
Disruption in SCFA production may be linked to the progression of Parkinson's disease.

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Neurodegeneration involves the progressive deterioration of neuronal structure and function, leading to deficits in cognition, motor skills, and other neurological processes. Parkinson's disease (PD) is notably prevalent among neurodegenerative disorders, characterized by dopaminergic neurodegeneration, protein misfolding, and an inflammatory brain environment. Despite advancements in understanding its pathophysiology, PD and other neurodegenerative conditions still lack effective disease-modifying therapies. This shortfall highlights the need for novel, multifactorial approaches to treatment. Recent research has spotlighted the as a significant player in neurological health, particularly through the activity of gut-derived (SCFAs). These microbial metabolites, primarily acetate, propionate, and butyrate, are produced via the fermentation of dietary fibers and are vital for maintaining intestinal and neural homeostasis. SCFAs exert anti-inflammatory effects, preserve blood-brain barrier integrity, and modulate neurotransmitter systems. Among them, butyrate shows notable neuroprotective capabilities, including histone deacetylase inhibition and mitochondrial enhancement. Disruption in SCFA production has been associated with PD progression, further underscoring their relevance. This review explores the mechanistic roles of SCFAs in modulating neurodegeneration, with an emphasis on PD. SCFA-based strategies offer a promising adjunctive route to restoring microbial balance, mitigating neuroinflammation, and safeguarding neurological function in neurodegenerative disorders.

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Abstract

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