Progressive neurodegenerative diseases, including Alzheimer's or Parkinson's disease afflict millions of people worldwide. The therapeutic possibilities for many patients, however, are limited and there is no causal therapy yet available. To address this unmet clinical need, it is important to gain more insight into the  molecular mechanisms that drive neurodegenerative disease pathology. Aging and associated neurodegenerative diseases display a severe mismatch between cell sensing and cell signaling. As a result of this, cells undergo drastic dynamic changes in their structure, motility and metabolism that ultimately lead to cell death. The signaling pathways of programmed cell death funnel into mitochondria, the key organelles of cell metabolism. The distribution and shape of mitochondria also change with functional demand, in response to environmental stimuli and energetic requirements. Metabolic cell flexibility is an essential characteristic of the cell, enabling it to adapt to nutrient availability, thus preserving mitochondrial function, promoting cell survival and increasing longevity.

Our research program is focused on the following themes:

•    Understanding the molecular mechanisms that link mitochondrial dysfunction with aging and neurodegeneration.

•    Understanding how mitochondrial dysfunction is associated with neuroinflammation.

•    Applying this knowledge in the development of new therapies to treat diseases linked to mitochondrial dysfunction.

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We investigate:

i) the role of potassium SK channels in mitochondrial metabolism and cell survival pathways.

We use either pharmacological tools or genetic modifications  to modulate SK channel activity and study their effects on calcium signaling (cytosolic and mitochondrial), mitochondrial respiration (by Seahorse technology or high-resolution respirometry) and cell survival of neuronal HT22 cells, human dopaminergic cells and microglia cells.

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ii) how alterations of mitochondrial calcium affects mitochondrial metabolism and cell survival in neurodegeneration.

We interfere with mitochondrial-ER contact sites either by strengthening their interaction or by depletion of proteins (GRP75) that enable this interaction. Mitochondrial calcium and the effects of this modulation on cell survival pathways are studied.