AI Article Synopsis
- Parkinson's disease (PD) is a rapidly growing neurological disorder characterized by the loss of dopamine-producing neurons, leading to both motor and non-motor symptoms, and current therapies do not halt disease progression.
- Emerging treatments focus on regenerating dopaminergic neurons through cell transplantation and innovative approaches like reprogramming astrocytes, despite challenges related to ethical concerns and cell sources.
- The review emphasizes advances in reprogramming astrocytes using transcription factors and miRNAs, and highlights potential neuroprotective strategies by targeting mitochondrial health and inflammation in astrocytes to combat PD.
Article Abstract
Parkinson's disease (PD) is currently the fastest growing disabling neurological disorder worldwide, with motor and non-motor symptoms being its main clinical manifestations. The primary pathological features include a reduction in the number of dopaminergic neurons in the substantia nigra and decrease in dopamine levels in the nigrostriatal pathway. Existing treatments only alleviate clinical symptoms and do not stop disease progression; slowing down the loss of dopaminergic neurons and stimulating their regeneration are emerging therapies. Preclinical studies have demonstrated that transplantation of dopamine cells generated from human embryonic or induced pluripotent stem cells can restore the loss of dopamine. However, the application of cell transplantation is limited owing to ethical controversies and the restricted source of cells. Until recently, the reprogramming of astrocytes to replenish lost dopaminergic neurons has provided a promising alternative therapy for PD. In addition, repair of mitochondrial perturbations, clearance of damaged mitochondria in astrocytes, and control of astrocyte inflammation may be extensively neuroprotective and beneficial against chronic neuroinflammation in PD. Therefore, this review primarily focuses on the progress and remaining issues in astrocyte reprogramming using transcription factors (TFs) and miRNAs, as well as exploring possible new targets for treating PD by repairing astrocytic mitochondria and reducing astrocytic inflammation.
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| http://dx.doi.org/10.1016/j.nbd.2023.106224 | DOI Listing |
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