Stem Cell Research has been the on the cutting edge of science, and become extremely useful for many neurodegenerative diseases like Parkinson’s Disease.
Parkinson’s disease (PD) is a common neurodegenerative disorder, defined by a selective loss of dopaminergic (DA) neurons in the substantia nigra, and the formation of lewy bodies. While common signs and symptoms include tremors, slowed movement, rigid muscles, and impaired balance, non-dopaminergic symptoms can include gait abnormality and dementia when the disease spreads to non-dopaminergic systems, and these can be increasingly challenging to treat. 60,000 American’s are diagnosed with Parkinson’s each year, with an estimated 10 million people living worldwide with this condition.
Recent research on Parkinson’s has concentrated on dissecting the neurological mechanism in order to discover therapeutic strategies. Protein breakdown, mitochondria dysfunction, oxidative stress and kinase pathways are implicated in PD, with many cellular and animal models having been established to unravel the mechanism behind PD. However these discoveries are not based on human neurons, and may not reflect several disease-causing factors present in human Parkinson’s disease.
Stem Cells
Stem cells are a growing field or research, and are a renewable source of tissue that can be coaxed to become different cell types in the body. The best-known examples are the embryonic stem (ES) cells found within an early-stage embryo. These cells can generate all the major cell types of the body. This form of research has drawn ethical concerns throughout the media for years, with the concern of abusing a potential human life form. However research involving Parkinson’s Disease and Stem Cells do not use this form of research, averting ethical concerns with regard to fetal tissues. Induced pluripotent stem cells (iPSCs) refer to a group of pluripotent stem cells that can be generated from adult cells. These cells share the same property as embryonic stem cells, to be able to differentiate into any tissue in the body. Numerous terminally differentiated cells can be used to generate iPSCs, avoiding destruction of an embryo. Sources of iPSCs include skin, liver and stomach cells. New breakthroughs in iPSCs include potentially programming iPSCs from a follicle of hair or a mouth swab.
Contributions of iPSCs
iPSCs have provided the opportunity to understand the PD mechanism in more detail, by doing pathological studies on live DA neurons. For example, a large break-through via iPSCs have connected mitophagy with PD. This complex mechanism involving PINK1 and Parkin enzymes has further cleared the event of decreased mitochondrial regulation with Parkinson’s Disease.
Therapeutics have also been developed through access of iPSCs. Coenzyme 10, rapamycin, and LRRK2 inhibitor are drugs found to alter cytotoxicity in neurons from patients with PD. Furthermore, it was found that these medications selectively reduced oxygen species production in neurons with the PINK1 mutation, clarifying the difference in susceptibility between diseased neurons and artificial disease models.
iPSCs have contributed to diagnosis methods. iPSCs derived from patients may serve this need if the phenotypes shownin iPSC-derived neurons exhibit pathological features in PD. This has further improved diagnostic accuracy of early PD.
Recent research has yielded encouraging results regarding cellular replacement. Some recent attempts transplanting dopamine neurons from rodent to primate was successful and produced increased cognition. Additionally, it was found iPSCs were able to differentiate into dopamine neurons and rescue motor deficits in a rat PD model. This was also repeated in a primate. Although this is relatively unexplored, these results provide a favorable outlook for the application of transplantation of iPSCs for PD treatment.
Overall, iPSC-derived neurons provide promise for PD modeling, and can be utilized for investigation of disease pathogenesis, diagnosis tools, and offer new therapeutics for patients.