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Targeting dysregulated IP3 receptor-mediated calcium signaling as an early event in Alzheimer’s disease through its Bcl-2-interaction network

Alzheimer’s disease, the most frequent form of dementia, has an enormous impact on the quality of life and society. At late stages, the disease is characterized by toxic protein aggregates (amyloid beta) and the demise of cells in the brain (neurons). While neuronal loss cannot be reverted, it is possible to delay this process. Thus, it is instrumental to focus on the early stages in Alzheimer’s disease development, with one of the key features being deranged calcium (Ca2+) signaling. This project will focus on the role of IP3 receptors, intracellular Ca2+ channels, and their modulation by Bcl-2, a major anti-cell death protein. Bcl-2 serves as an inhibitor of IP3 receptors keeping these channels in check. The question is whether alterations in IP3 receptor / Bcl-2-complex formation and modulation could underlie Ca2+-signaling dysregulation in Alzheimer’s disease. In addition, the properties of Bcl-2 proteins in inhibiting IP3 receptors could be exploited to prevent or at least delay Alzheimer’s disease features by supporting memory function, maintaining neuronal morphology and sustaining neuronal survival. Thanks to the complementary expertise of its partners, the project will apply an integrated approach, from biochemical & cell biological studies at the (sub)cellular level to ex vivo work in brain samples and in vivo studies in mice.

Date:21 Sep 2020 →  Today
Keywords:Alzheimer's disease, Bcl-2 protein, Ca2+ signaling
Disciplines:Cell signaling, Neurological and neuromuscular diseases
Project type:PhD project