Abstract
Parkinson’s disease (PD) is one of the most common neurodegenerative disease characterized by a specific and progressive loss of dopaminergic (DA) neurons and dopamine, causing motor dysfunctions and impaired movements. Unfortunately, available therapies can partially treat the motor symptoms, but they have no effect on non-motor features. In addition, the therapeutic effect reduces gradually, and the prolonged use of drugs leads to a significative increase in the number of adverse events. For these reasons, an alternative approach that allows the replacement or the improved survival of DA neurons is very appealing for the treatment of PD patients and recently the first human clinical trials for DA neurons replacement have been set up. Here, we review the role of chemical and biological molecules that are involved in the development, survival and differentiation of DA neurons. In particular, we review the chemical small molecules used to differentiate different type of stem cells into DA neurons with high efficiency; the role of microRNAs and long non-coding RNAs both in DA neurons development/survival as far as in the pathogenesis of PD; and, finally, we dissect the potential role of exosomes carrying biological molecules as treatment of PD.
Highlights
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, with an increasing incidence worldwide and a great effort for the health care resources [1,2].At cellular level, PD is characterized by an irreversible and progressive loss of midbrain dopaminergic (DA) neurons in the substantia nigra pars compacta: this degeneration leads to the dysregulation of the nigrostriatal pathway that causes the manifestation of the clinical motor symptoms associated with PD [3,4].Current therapeutic options for PD aim to support the nigrostriatal pathway administrating drugs that are able either to modulate the DA transmission or increase the dopamine level in the brain [3]
The first study that highlighted the link between miRNAs dysregulation and PD onset was performed by Kim et al They reported that mice with a deletion of Dicer had a progressive loss of midbrain DA neurons accompanied by a reduction of mobility, suggesting that Dicer is fundamental for DA neuron differentiation and maintenance [21]
Data obtained from this study showed that rats receiving the Vascular endothelial growth factor (VEGF)-containing capsules exhibit a significant reduction of rotational behavior and an increase of TH+ fibers, suggesting that VEGF might have an efficacy in the PD treatment [131]
Summary
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, with an increasing incidence worldwide and a great effort for the health care resources [1,2]. These pharmacological treatments are only able to alleviate the physical symptoms, sometime delaying the disease progression [5], and their efficacy gradually reduces over the time [6] For these reasons, an alternative approach with the aim to replace the degenerated cells with stem cell-derived DA neurons is appealing. Biomedicines 2021, 9, 754 to alleviate the physical symptoms, sometime delaying the disease progression [5], and their efficacy gradually reduces over the time [6]
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