Molecular mechanisms underlying Parkinson's disease and role of phytochemicals, α-synuclein, sirtuins, and incretin mimetics in potential therapy.
Molecular mechanisms underlying Parkinson's disease and role of phytochemicals, α-synuclein, sirtuins, and incretin mimetics in potential therapy.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
US · Author affiliation · country only
Behavioral Services, Anderson Center for Autism, Staatsburg, NY, United States.Location evidence
Coleraine, GB · Author affiliation
Centre for Diabetes Research, School of Biomedical Sciences, Ulster University, Coleraine, United Kingdom.Location evidence
NP · Author affiliation · country only
Department of Pharmacology, National Medical College and Teaching Hospital, Birgunj, Nepal.Location evidence
Dhaka, BD · Author affiliation
Department of Pharmacy, School of Pharmacy and Public Health, Independent University, Bangladesh (IUB), Dhaka, Bangladesh.Location evidence
Glasgow, GB · Author affiliation
Natural Products Research Laboratory, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.Location evidence
New Orleans, US · Author affiliation
Department of Microbiology and Immunology, Tulane University, New Orleans, LA, United States.Location evidence
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Original abstract
Parkinson's disease (PD) is a progressive neurodegenerative disorder primarily characterized by dopaminergic neuronal loss in the substantia nigra and intracellular accumulation of misfolded α-synuclein aggregates. Despite being extensively studied, current pharmacological and surgical interventions remain mostly symptomatic, leaving limited efficacy in halting or reversing disease progression. The complicated pathogenesis of PD involves oxidative stress, mitochondrial dysfunction, neuroinflammation, impaired autophagy, and proteostasis imbalance, altogether contributing to neuronal vulnerability. In addition to established drugs such as levodopa, other medications affecting dopamine pathways and incretin mimetics, numerous studies have highlighted the therapeutic potential of phytomolecules to target these processes. This includes resveratrol, curcumin, quercetin, baicalein, berberine and epigallocatechin gallate (EGCG), which have demonstrated pleiotropic neuroprotective effects by mitigating oxidative and inflammatory cascades, improving mitochondrial biogenesis, preventing proteostasis imbalance, and/or blocking α-synuclein aggregation. Some phytomolecules may also act through the sirtuin and PI3K/Akt signaling pathways, linking neuroprotection with metabolic regulation. Some phytomolecules may additionally alleviate insulin resistance and stimulate incretin (GLP-1/GIP) secretion, potentially enhancing their neuroprotective. The exact relationship between αS, sirtuins, insulin signaling and phytomolecules is not yet fully understood. Nevertheless, increasing evidence suggests that phytomolecules can modulate brain insulin resistance and enhance incretin signaling, which contribute to their neuroprotective effects in PD. This review highlights the interconnected metabolic and neuronal mechanisms in Parkinson's disease encompassing α-synuclein pathology, sirtuin imbalance, and disrupted insulin signaling role in PD and explores incretin and phytomolecules molecule based therapies, often utilized for type 2 diabetes management as complementary multi-target neuroprotective strategies.