Gut–Brain Axis in Focus: Polyphenols, Microbiota, and Their Influence on α-Synuclein in Parkinson’s Disease

Nutrients, Journal Year: 2024, Volume and Issue: 16(13), P. 2041 - 2041

Published: June 27, 2024

With the recognition of importance gut-brain axis in Parkinson's disease (PD) etiology, there is increased interest developing therapeutic strategies that target α-synuclein, hallmark abhorrent protein PD pathogenesis, which may originate gut. Research has demonstrated inhibiting aggregation, oligomerization, and fibrillation α-synuclein are key for modification. Polyphenols, rich fruits vegetables, drawing attention their potential role this context. In paper, we reviewed how polyphenols influence composition functional capabilities gut microbiota resulting microbial metabolites potentially enhance modulation aggregation. Understanding interaction between identifying specific microbes efficacy crucial precision nutrition based on microbiome.

Language: Английский

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α-Synuclein Targeted Therapy with Multiple Pathological Improvement for Parkinson’s Disease by Macrocyclic Amphiphile Nanomedicine

Biomaterials, Journal Year: 2025, Volume and Issue: 322, P. 123378 - 123378

Published: April 25, 2025

Language: Английский

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Mapping the Structural Landscape of Amyloid Fibrils to Guide Polymorph-Specific Therapeutics

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: May 14, 2025

Abstract Amyloid fibrils are pathological hallmarks of neurodegenerative diseases and central contributors to their progression, representing promising targets for disease-modifying interventions. However, limited access patient-derived the inability reproduce folds in vitro hinder development fibril-specific ligands. Here, we present FibrilSite, a computational pipeline that identifies geometric physicochemical similarities across fibril surfaces demonstrate its utility identify structural features distinguish different polymorphs. Our analysis uncovered conserved polymorph-specific within alpha-synuclein fibrils. Notably, one site was between ex vivo multiple system atrophy H50Q mutant fibrils, suggesting latter’s potential drug discovery. Druggability predictions further prioritized ligandable sites Together, our findings establish structure-based framework identifying disease-relevant mapping them onto suitable models, guiding rational diagnostics therapeutics amyloid-related disorders with improved translational potential.

Language: Английский

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The 75–99 C-Terminal Peptide of URG7 Protein Promotes α-Synuclein Disaggregation

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1135 - 1135

Published: Jan. 17, 2024

Up Regulation Gene seven (URG7) is the pseudogene 2 of transporter ABCC6. The translated URG7 protein localized with its single transmembrane α-helix in endoplasmic reticulum (ER) membrane, orienting N- and C-terminal regions lumen cytoplasm, respectively, it plays a crucial role folding ER proteins. Previously, region (PU, residues 75–99) has been shown to modify aggregation state α-synuclein lysate HepG2 cells. PU analogs were synthesized, their anti-aggregation potential was tested vitro on obtained using recombinant DNA technology. Circular dichroism (CD), differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, microscopic techniques used assess sample’s behavior. results show that peptides studied by themselves are prone clathrate-like structure formation variable stability. Aggregation accompanied desolvation peptide chain an increase intermolecular β-sheets. all interact aggregates those possessing most stable structures have highest disaggregating effect. These findings suggest may interacting modulating could be generate interesting therapeutic candidates as disaggregators α-synuclein.

Language: Английский

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Chemistry in Ukraine

The Chemical Record, Journal Year: 2024, Volume and Issue: 24(2)

Published: Jan. 29, 2024

Abstract In this special issue, we highlight recent advances in chemical research by scientists Ukraine, as well their compatriots and collaborators outside the country. Besides spotlighting contributions, see our task fostering global partnerships multi‐, inter‐, trans‐disciplinary collaborations, including much‐needed co‐funded projects initiatives. The three decades of renewed Ukraine independence have seen rather limited integration Ukrainian (chemical) science into communities. [1] At same time, surge collaborative initiatives between European Union (EU) echoes unfolding steps towards Ukraine's full participation to Horizon Europe Program. This recently implemented step opens enormous possibilities for researchers apply diverse EU grants. Moreover, a number journal issues collections were launched chemistry (i. e., Chemistry Heterocyclic Compounds [2] ChemistrySelect [3] ). Other scientific include ‘European School Ukrainians’ [4] ‘Kharkiv Chemical Seminar’ [5] voluntary aimed at engaging international research.

Language: Английский

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A Plant Model of α-Synucleinopathy: Expression of α-Synuclein A53T Variant in Hairy Root Cultures Leads to Proteostatic Stress and Dysregulation of Iron Metabolism

Applied Biosciences, Journal Year: 2024, Volume and Issue: 3(2), P. 233 - 249

Published: May 20, 2024

Synucleinopathies, typified by Parkinson’s disease (PD), entail the accumulation of α-synuclein (αSyn) aggregates in nerve cells. Various αSyn mutants, including A53T variant linked to early-onset PD, increase propensity for aggregate formation. In addition disrupting protein homeostasis and inducing proteostatic stress, aggregation PD is associated with an imbalance iron metabolism, which increases generation reactive oxygen species causes oxidative stress. This study explored impact expression transgenic hairy roots four medicinal plants (Lobelia cardinalis, Artemisia annua, Salvia miltiorrhiza, Polygonum multiflorum). all tested plants, triggered proteotoxic stress perturbed homeostasis, mirroring molecular profile observed human animal common eukaryotic defense mechanisms against stresses, a plant response generally includes biosynthesis diverse set protective secondary metabolites. Therefore, root cultures expressing offer platform identifying metabolites that can ameliorate effects αSyn, thereby aiding development possible treatments and/or synucleinopathies.

Language: Английский

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A Perspective on Interdicting in Protein Misfolding for Therapeutic Drug Design: Modulating the Formation of Nonlocal Contacts in α-Synuclein as a Strategy against Parkinson’s Disease

The Journal of Physical Chemistry B, Journal Year: 2024, Volume and Issue: 128(27), P. 6439 - 6448

Published: June 28, 2024

In recent work we proposed that interdiction in the earliest contact-formation events along folding pathway of key viral proteins could provide a novel avenue for therapeutic drug design. this Perspective explore potential applicability protein strategy realm neurodegenerative diseases with specific focus on synucleinopathies. order to fulfill goal review proposal and its practical challenges, present new results concerning design strategies possible peptide drugs be useful preventing α-synuclein aggregation.

Language: Английский

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Piperonal protects neuron-like and retinalpigment epithelial (RPE) cells from oxidative stress and apoptosis through inhibition of α-synuclein aggregation

Arabian Journal of Chemistry, Journal Year: 2024, Volume and Issue: 17(10), P. 105982 - 105982

Published: Aug. 29, 2024

Language: Английский

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