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Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease and the prevalence of it has increased worldwide. PD causes severe damage to loss of midbrain dopaminergic neurons (DN) at substantia nigra which involves in the movement control. The synaptic terminals of DNs are destroyed in the posterior putamen. PD is also characterized by accumulation of misfolded and amyloid α-synuclein into proteinous inclusions named Lewy bodies. So far there is no effective treatment for PD and approved medications for PD can only slow down clinical progression, control motor and non-motor symptoms. Currently, the approved medications just induce the release of dopamine and prevent the release of acetylcholine from nerve terminals of caudate cholinergic interneurons and it is necessary to provide more effective treatment methods in the early stages of the disease. Significant progress has been achieved in development of drugs that can reduce neuronal cell death and lead up to neuroprotection, however targeting delivery of drugs to improve the pharmaceutical effects of drugs is remained as a challenge. Therefore, there is a pressing demand to find practical strategies for delivering these pharmaceuticals in vivo through the BBB without disrupting the brain's functions. In this regard, Focused ultrasound (FUS) technology eliminates the need for brain surgery and temporarily opens the blood-brain barrier to allow drugs to pass through. In this review, the application of FUS as a new drug delivery application in the PD models and the potential clinical application of neuroprotective agents are provided briefly.
 

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Objective: Alpha-synuclein is a major component of protein plaques in synucleinopathies, particularly Parkinson’s disease. The purpose of this study is to assess the inhibitory effects of cuminaldehyde on the fibrillation of alpha-synuclein. Methods: Alpha-synuclein was expressed in Escherichia coli and subsequently purified. For the process of fibrillation, purified protein was incubated at 37^◦C and pH 7.2. Fibrillation was analyzed by the standard fibril methods. The effects of different concentrations of cuminaldehyde (20-500 μM) on alpha-synuclein fibrillation were studied by assessment of the cytotoxic effects of samples on the neuroblastoma cell line, SK-N-MC. To study the protein aggregation forms that were generated in the presence of cuminaldehyde, SDS resistance and induced fibrillation (seeding) methods were employed. For studying its specificity on alpha-synuclein, the effect of cuminaldehyde on lysozyme fibrillation was also examined. Results: We showed, for the first time, that cuminaldehyde inhibited fibrillation by more than 80%. The highest inhibition was observed at the ratio of 5-15 moles of drug to protein. The viability of the treated cells with inhibited proteins was more than 90%, whereas non-inhibited samples caused a decrease in viability by 50%. Inhibited samples were not resistant to SDS and they were unable to induce fibrillation. Cuminaldehyde did not inhibit lysozyme fibrillation. Conclusion: Cuminaldehyde inhibited fibrillation of alpha-synuclein which was accompanied by small amorphous aggregated particles of alpha synuclein. The inhibited protein samples did not induce aggregation. Thus, cuminaldehyde can be considered as a candidate to inhibit the formation of alpha-synuclein plaques.