Delineating the Mechanistic Insight of Inhibition of α-Synuclein Fibrillation by Neuro Metabolite, Myo-inositol: Implications in Synucleopathies-Related Disorders

ACS Chemical Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

The fibrillation of α-synuclein (α-syn) is a major factor contributing to neuronal damage and critical in developing synucleopathies-related disorders. Considering this, the discovery new compounds that can inhibit or modulate α-syn aggregation significant area research. While polyol osmolytes have been shown reduce fibrillation, impact brain metabolites such as myo-inositol (MI) on has not yet explored. This study first examine effects MI aggregation, utilizing spectroscopic, microscopic, cell cytotoxicity assay. Various assays revealed inhibits dose-dependent manner. Fluorescence microscopy observations suggest by forming amorphous aggregates. MTT assay aggregates presence different concentrations were toxic compared fibrils. Thus, mechanistic insight inhibition was explored employing interaction studies using calorimetric, silico approaches. Surface plasmon resonance isothermal titration calorimetry MI-α-syn interacted with binding affinity, reaction spontaneous. Molecular docking results depict aggregation-prone residues (36-42) at N-terminal α-syn, thereby stabilizing preventing fibril formation. dynamics simulation demonstrate stability complex formation α-syn. highlighted from amyloid fibril, which could be further for therapeutic management

Language: Английский

Emerging Biomarkers in Metabolomics: Advancements in Precision Health and Disease Diagnosis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 13190 - 13190

Published: Dec. 8, 2024

Metabolomics has come to the fore as an efficient tool in search for biomarkers that are critical precision health approaches and improved diagnostics. This review will outline recent advances biomarker discovery based on metabolomics, focusing metabolomics reported cancer, neurodegenerative disorders, cardiovascular diseases, metabolic health. In provides evidence unique oncometabolites important early disease detection monitoring of treatment responses. Metabolite profiling conditions such mental disorders can offer diagnosis mechanisms into especially Alzheimer's Parkinson's diseases. addition these, lipid other metabolites relating promising patient stratification personalized treatment. The gut microbiome environmental exposure also feature among influential factors because they sculpt individual profiles, impacting overall Further, we discuss technological current clinical applications, challenges faced by validation toward medicine. Finally, this discusses future opportunities regarding integration routine healthcare enable preventive approaches.

Language: Английский