Mechanisms of GBA1 related PD in hiPSC derived neurons

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dc.contributor.advisor Gasser, Thomas (Prof. Dr.) Schöndorf, David 2018-09-19T07:20:43Z 2018-09-19T07:20:43Z 2018-09-19
dc.identifier.other 511167245 de_DE
dc.identifier.uri de_DE
dc.description.abstract Parkinson's Disease (PD) is the second most common neurodegenerative disorder after Alzheimers Disease affecting approximately 5% of the population over 80 years of age. The exact mechanisms underlying the disease are not known but environmental as well as genetic factors have been described to contribute to the disease progression. Mutations in the gene GBA1 which encodes for the protein Glucoerebrosidase 1 (GCase) represent the most common genetic risk factor to develop PD and lead to reduced activity of the enzyme GCase. Importantly, considering the clinical representation, GBA1 related PD is similar to sporadic forms of the disease, making underlying mechanisms an interesting target to develop treatment strategies for PD. In the current work we investigate such underlying mechanisms using induced pluripotent stem cell (iPSC) derived neurons from PD patients with GBA1 mutations. We find that such neurons resemble PD associated features like loss of GCase activity, accumulation of alpha synuclein,disturbances in autophagy and calcium homeostasis as well as mitochondrial dysfunction. Finally, we show that application of the Nicotinamid adenosine dinucleotide (NAD) precursor Nicotinamid riboside (NR) partly rescues such defects in iPSC derived neurons as well as in vivo models of PD, making the NAD metabolism a promising target for the treatment of PD. en
dc.language.iso en de_DE
dc.publisher Universität Tübingen de_DE
dc.rights ubt-podok de_DE
dc.rights.uri de_DE
dc.rights.uri en
dc.subject.classification Stammzelle , Nervenzelle , Parkinson-Krankheit de_DE
dc.subject.ddc 500 de_DE
dc.subject.ddc 570 de_DE
dc.subject.ddc 610 de_DE
dc.subject.other ipsc en
dc.subject.other stem cells en
dc.subject.other neurodegeneration en
dc.subject.other GBA1 en
dc.title Mechanisms of GBA1 related PD in hiPSC derived neurons de_DE
dc.type Dissertation de_DE
dcterms.dateAccepted 2018-07-18
utue.publikation.fachbereich Medizin de_DE
utue.publikation.fakultaet 4 Medizinische Fakultät de_DE


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