Unlocking Neuroprotection: How Chebulinic Acid Targets Protein Biomarkers and Lipid Imbalance in Alzheimer’s Disease

Overview

Alzheimer’s disease (AD), a neurodegenerative disorder causing cognitive deterioration, remains a leading cause of death. Previous research has looked into the effects of amyloid-beta (Aβ) and genetic and bacterial risk factors - specifically apolipoprotein E4 (ApoE4) and lipopolysaccharide (LPS) - as factors behind lipid droplet (LD) formation in AD. This study aims to determine the specific effects of these molecules on lipid dysregulation in AD. It also investigates the efficacy of chebulinic acid (CA), a natural plant-based chemical, as potential treatment for AD. Molecular docking revealed strong binding affinities for Aβ with the acyl -CoA synthetase long - chain (ACSL) family, suggesting ACSL’s role in LD formation. CA also demonstrated properties similar to Triacsin C, an inhibitor of the ACSLs, indicating its potential to prevent LD production. CA reduced cell adhesion and therefore neuroinflammation caused by Aβ and LPS. Both AB and LPS caused an imbalance in LD formation, harming storage cells and structures. By reducing lipid production and LD formation, CA mitigated the harmful lipid dysregulation caused by Aβ and LPS. Aβ and LPS further disrupted ApoE balance, differentially promoting harmful ApoE4 expression while decreasing production of more protective ApoE alleles. CA prevented the upregulation of ApoE4. In a Drosophila model, both Aβ and ApoE4 impaired locomotion, demonstrating further lipid dysfunction, while CA consistently improved movement, indicating broad therapeutic benefits. Overall, this study clarifies the specific roles of Aβ, LPS, and ApoE4 in AD lipid dysregulation and highlights CA as a promising candidate for AD treatment, counteracting multiple disease - promoting factors. Investigating Hand Dexterity Improvement in Individuals with Traumatic Brain Injury using Targeted Neuromodulation Combined with Music-based Exergaming: A double-