Cellular and Molecular Aspects of Parkinson Treatment: Future Therapeutic Perspectives

Abstract

Parkinson’s disease is a neurodegenerative disorder accompanied by depletion of dopamine and loss of dopaminergic neurons in the brain that is believed to be responsible for the motor and non-motor symptoms in this disease. The main drug prescribed for Parkinsonian patients is l-dopa, which can be converted to dopamine by passing through the blood-brain barrier. Although l-dopa is able to improve motor function and improve the quality of life in the patients, there is inter-individual variability and some patients do not achieve the therapeutic effect. Variations in treatment response and side effects of current drugs have convinced scientists to think of treating Parkinson’s disease at the cellular and molecular level. Molecular and cellular therapy for Parkinson’s disease include (i) cell transplantation therapy with human embryonic stem (ES) cells, human induced pluripotent stem (iPS) cells and human fetal mesencephalic tissue, (ii) immunological and inflammatory therapy which is done using antibodies, and (iii) gene therapy with AADC-TH-GCH gene therapy, viral vector-mediated gene delivery, RNA interference-based therapy, CRISPR-Cas9 gene editing system, and alternative methods such as optogenetics and chemogenetics. Although these methods currently have a series of challenges, they seem to be promising techniques for Parkinson’s treatment in future. In this study, these prospective therapeutic approaches are reviewed.

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Correspondence to Amirhossein Sahebkar.

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Key Message

The new therapeutic approaches described in this study include cell transplantation, gene therapy and immunotherapy, and are promising strategies for effective PD therapy in the near horizon.

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Jamebozorgi, K., Taghizadeh, E., Rostami, D. et al. Cellular and Molecular Aspects of Parkinson Treatment: Future Therapeutic Perspectives. Mol Neurobiol 56, 4799–4811 (2019). https://doi.org/10.1007/s12035-018-1419-8

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Keywords

  • Parkinson’s disease
  • Transplantation therapy
  • Molecular mechanisms
  • l-dopa
  • Gene therapy