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Grant on Alzheimer`s disease iPSC research

Thursday, 13 December 2018

End of November the research proposal The role of potassium SK channels in Alzheimer`s disease was awarded by Alzheimer Nederland. Amalia Dolga from the University of Groningen (RUG) will work on this project together with Steven Kushner (ErasmusMC) and Alex Domling (RUG).

"Several hypothesis tried to explain the molecular pathways of brain degeneration in Alzheimer`s Disease (AD), however a general consensus is largely missing and therefore, clinical trials largely failed to demonstrate a cure against AD," Amalia Dolga explains. In AD patients, brain degeneration is accompanied by altered cell excitability and mitochondrial dysfunction, besides Amyloid beta and tau toxicity. An emerging hypothesis in AD points towards a critical role of ion channels in brain cell function, by regulating neuronal firing, cell metabolism, protein aggregation, and cell death. "Normalizing" ion channels could therefore re-enable neuronal firing, restore cell metabolism, and ultimately prevent cell death.

"Our proposal addresses exactly this and aims at working on an important question in the field of AD and channelopathies," Amalia Dolga says. "Recently, our group has shown that calcium-activated potassium (SK) channels prevent cell damage by regulating both excitability and mitochondrial dysfunction. This proposal investigates how regulation of SK channels affect cell survival pathways of human-induced pluripotent stem cells derived from familial AD patients. We will use iPSC-derived neurons, and analyze their cell metabolism and neuronal excitability. By modulating the function of potassium channels, we aim to reinstate neuronal function and mitochondrial respiration in AD neurons. This will be achieved by a unique combination of cell biology, chemistry and neuroscience."

The project will run for two years and is funded by the Alzheimer Nederland with 100.000 E.

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