The role of exosomes in pathogenesis and the therapeutic efficacy of mesenchymal stem cell-derived exosomes against Parkinson's disease.

Parkinson's disease (PD) is a chronic, progressive, neurodegenerative disease. The predominant pathology of PD is the loss of dopaminergic cells in the substantia nigra. Cell transplantation is a strategy with significant potential for treating PD; mesenchymal stem cells (MSCs) are a tremendous therapeutic cell source because they are easily accessible. MSC-derived exosomes with potential protective action in lesioned sites serve as an essential promoter of neuroprotection, and neurodifferentiation, by modulating neural stem cells, neurons, glial cells, and axonal growth in vitro and in vivo environments. The biological properties of MSC-derived exosomes have been proposed as a beneficial tool in different pathological conditions, including PD. Therefore, in this review, we assort the current understanding of MSC-derived exosomes as a new possible therapeutic strategy for PD by providing an overview of the potential role of miRNAs as a component of exosomes in the cellular and molecular basis of PD.

Targeting Mitochondria as a Therapeutic Approach for Parkinson's Disease.

Neurodegeneration is among the most critical challenges that involve modern societies and annually influences millions of patients worldwide. While the pathophysiology of Parkinson's disease (PD) is complicated, the role of mitochondrial is demonstrated. The in vitro and in vivo models and genome-wide association studies in human cases proved that specific genes, including PINK1, Parkin, DJ-1, SNCA, and LRRK2, linked mitochondrial dysfunction with PD. Also, mitochondrial DNA (mtDNA) plays an essential role in the pathophysiology of PD. Targeting mitochondria as a therapeutic approach to inhibit or slow down PD formation and progression seems to be an exciting issue. The current review summarized known mutations associated with both mitochondrial dysfunction and PD. The significance of mtDNA in Parkinson's disease pathogenesis and potential PD therapeutic approaches targeting mitochondrial dysfunction was then discussed.

The effects of betulinic acid chronic administration on the motor, non-motor behaviors, and globus pallidus local field potential power in a rat model of hemiparkinsonism.

Objectives: Parkinson's disease (PD) is a neurodegenerative disorder involving the central nervous system associated with motor and non-motor impairments. Betulinic acid (BA) is a natural substance considered an antioxidative agent. This study aimed to investigate the therapeutic potential of BA on motor dysfunctions and globus pallidus (GP) local EEG power in a 6-hydroxydopamine (6-OHDA)-induced rat model of hemiparkinsonism. Materials and Methods: Adult Wistar rats were categorized into different groups, containing; Sham, PD, and treated groups including different doses of BA (0.5, 5, and 10 mg/kg, IP), and L-dopa (20 mg/kg, PO, as positive control). The lesion was induced in the right medial forebrain bundle by injection of 6-OHDA (20 µg/kg). The treatment was begun just after the approved rotational test induced by apomorphine, 14 days after 6-OHDA administration. Motor behaviors such as catalepsy and stride-length and non-motor responses, including GP local EEG, were then assessed. Also, the levels of GSH, catalase, and concentration of dopamine in the brain tissue were measured. Results: Treatment of hemiparkinsonian rats with BA significantly improved catalepsy and stride-length (P<0.001 and P<0.01, respectively) and GP frequency bands' powers (P<0.001). Moreover, the activities of GSH (P<0.001), catalase (P<0.001), and the concentration of dopamine (P<0.001) in the brain were increased. Conclusion: Current results proved the potent ability of BA to scavenge free radicals and to remove oxidative agents in the brain tissue. This natural product could be considered a possible therapeutic compound for motor and non-motor disorders in PD.