alpha-synuclein and ferulic-acid

Parkinson's disease (PD) is a complex neurological disorder characterized by motor and nonmotor features. Although some drugs have been developed for the therapy of PD in a clinical setting, they only alleviate the clinical symptoms and have yet to show a cure. In this study, by employing the

Topics: alpha-Synuclein; Animals; Apoptosis; Autophagy; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Coumaric Acids; Dopaminergic Neurons; Gene Knockdown Techniques; Hydrogen Peroxide; Locomotion; Neuroprotective Agents; Oxidopamine; Parkinson Disease; PC12 Cells; Rats; Reactive Oxygen Species; RNA Interference; Signal Transduction

This study investigated the effects of ferulic acid (FR), muscle exercise (Ex) and combination of them on rotenone (Rot)-induced Parkinson disease (PD) in mice as well as their underlying mechanisms.. 56 male C57BL/6 mice were allocated into 8 equal groups, 1) Normal control (CTL), 2) FR (mice received FR at 20 mg/kg/day), 3) Ex (mice received swimming Ex) and 4) Ex + FR (mice received FR and Ex), 5) Rot (mice received Rot 3 mg/Kg i.p. for 70 days), 6) ROT+ FR (mice received Rot + FR at 20 mg/kg/day), 7) ROT+ Ex (mice received Rot + swimming Ex) and 8) ROT+ Ex + FR (mice received Rot + FR and Ex). ROT group showed significant impairment in motor performance and significant reduction in tyrosine hydroxylase (TH) density and Hsp70 expression (p< 0.05) with Lewy bodies (alpha synuclein) aggregates in corpus striatum. Also, ROT+FR, ROT+EX and ROT + Ex+ FR groups showed significant improvement in behavioral and biochemical changes, however the effect of FR alone was more potent than Ex alone (p< 0.05) and addition of Ex to FR caused no more significant improvement than FR alone.. We concluded that, FR and Ex improved the motor performance in rotenone-induced PD rodent model which might be due to increased Hsp70 expression and TH density in corpus striatum and combination of both did not offer more protection than FR alone.

Topics: alpha-Synuclein; Animals; Coumaric Acids; Disease Models, Animal; HSP70 Heat-Shock Proteins; Male; Neuroprotection; Neuroprotective Agents; Parkinson Disease; Physical Conditioning, Animal; Substantia Nigra

Lewy bodies, mainly composed of α-synuclein (αS), are pathological hallmarks of Parkinson's disease and dementia with Lewy bodies. Epidemiological studies showed that green tea consumption or habitual intake of phenolic compounds reduced Parkinson's disease risk. We previously reported that phenolic compounds inhibited αS fibrillation and destabilized preformed αS fibrils. Cumulative evidence suggests that low-order αS oligomers are neurotoxic and critical species in the pathogenesis of α-synucleinopathies. To develop disease modifying therapies for α-synucleinopathies, we examined effects of phenolic compounds (myricetin (Myr), curcumin, rosmarinic acid (RA), nordihydroguaiaretic acid, and ferulic acid) on αS oligomerization. Using methods such as photo-induced cross-linking of unmodified proteins, circular dichroism spectroscopy, the electron microscope, and the atomic force microscope, we showed that Myr and RA inhibited αS oligomerization and secondary structure conversion. The nuclear magnetic resonance analysis revealed that Myr directly bound to the N-terminal region of αS, whereas direct binding of RA to monomeric αS was not detected. Electrophysiological assays for long-term potentiation in mouse hippocampal slices revealed that Myr and RA ameliorated αS synaptic toxicity by inhibition of αS oligomerization. These results suggest that Myr and RA prevent the αS aggregation process, reducing the neurotoxicity of αS oligomers. To develop disease modifying therapies for α-synucleinopathies, we examined effects of phenolic compounds on α-synuclein (αS) oligomerization. Phenolic compounds, especially Myricetin (Myr) and Rosmarinic acid (RA), inhibited αS oligomerization and secondary structure conversion. Myr and RA ameliorated αS synaptic toxicity on the experiment of long-term potentiation. Our results suggest that Myr and RA prevent αS aggregation process and reduce the neurotoxicity of αS oligomers. Phenolic compounds are good candidates of disease modifying drugs for α-synucleinopathies.

Topics: alpha-Synuclein; Amyloid; Animals; Antioxidants; Cinnamates; Circular Dichroism; Coumaric Acids; Curcumin; Depsides; Drug Evaluation, Preclinical; Flavonoids; Hippocampus; Long-Term Potentiation; Masoprocol; Mice; Microscopy, Atomic Force; Models, Molecular; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Phenols; Polymerization; Protein Structure, Secondary; Rosmarinic Acid