# Interactions Between Nutraceuticals and α-Synuclein Conformational States: Molecular Mechanisms and Neuroprotective Implications in Parkinson’s Disease

## TL;DR

This review explores how nutraceuticals can influence α-synuclein behavior in Parkinson’s disease, offering potential neuroprotective benefits.

## Contribution

The paper provides a comprehensive analysis of nutraceutical mechanisms targeting α-synuclein conformational states and barriers to clinical translation.

## Key findings

- Nutraceuticals like polyphenols and ginsenosides can suppress toxic α-synuclein oligomers.
- Poor bioavailability and blood–brain barrier limitations hinder clinical use of nutraceuticals.
- Advanced delivery systems may improve the neuroprotective potential of these compounds.

## Abstract

Synucleinopathies, including Parkinson’s disease (PD), are neurodegenerative disorders characterized by aberrant aggregation of α-synuclein (α-syn), a presynaptic protein with an intrinsic disorder nature. The transition of soluble monomers into oligomeric and fibrillar species represents a key molecular event driving neuronal dysfunction and neurodegeneration. Emerging evidence suggests that nutraceuticals, bioactive compounds derived from dietary sources, can modulate α-syn aggregation at multiple conformational stages. Polyphenols, alkaloids, ginsenosides, and food-derived peptides interfere with α-syn structure and assembly, suppressing the formation of toxic oligomer species and promoting the clearance of misfolded assemblies. Despite this potential, clinical translational of nutraceuticals is currently limited by poor systemic bioavailability and restricted central nervous system penetration due to blood–brain barrier constraints, which have largely confined research to preclinical studies. In this context, this review summarizes current knowledge of nutraceutical interventions targeting the conformational landscape of α-syn and highlighting both direct and indirect molecular mechanisms with involved in aggregation-prone species. Furthermore, we critically examine key challenges related to bioavailability and clinical translation, focusing on advanced delivery systems and precision-based approaches to enhance neuroprotective efficacy and support the potential of nutraceuticals as novel or adjunctive therapeutic strategies for PD.