FORIPS

BAVARIAN RESEARCH NETWORK INDUCED PLURIPOTENT STEM CELLS

Mitochondrial function in induced pluripotent stem cells (iPS) and thereof derived dopaminergic neurons of patients with Parkinson´s Disease

Field of work:

Idiopathic Parkinson's disease is a multifactorial disease. Among the causative factors are aging, genetic factors, but also environmental factors such as exposure to toxins. In particular toxins which inhibit the mitochondrial respiratory chain have been implicated in the pathogenesis of Parkinson´s disease. Therefore, mitochondrial dysfunction is thought to play a center role in the pathoetiology of the disease. In addition, work on the genetic forms of the disease in cell lines and animal models have supported this theory. To further support this hypothesis, however, human models, specifically based on midbrain dopaminergic neurons have been missing. In Parkinson´s Disease specifically this neuronal cell population is highly vulnerable and succumbs to cell death during the course of the disease. With the the lately available reprogramming technology it is now possible to generate such cellular models (induced pluripotent stem cells - iPSZ ) and examine both early and late changes in these Parkinson's disease patient-derived cells. In this project, these induced pluripotent stem cells and thereof differentiated neurons are examined concerning the following phenotypes:
(1) changes in the ability to differentiate into functional dopaminergic neurons of the midbrain,
(2 ) changes of mitochondrial parameters such as mitochondrial mass , - morphology - dynamics , and motility in iPSZ and thereof differentiated young and old neurons, (3) changes of mitochondrial functions and metabolic products, and last
(4) we want to determine the influence of known risk factors ( mitochondrial toxins, but also genetic risk factors) on the cellular disease process.
The envisioned new findings on mitochondrial functionality in human models and their effect on dopaminergic neurons will result in new approaches for therapeutic strategies but will also be important for early detection and diagnosis of idiopathic Parkinson's disease.

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