prof. dr. A.M. Dolga

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 in 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 to 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.

Current PhD projects under my supervision:

• Asmaa Oun: The role of LRKK2 in mitochondrial metabolism and inflammation.

(Co-supervision with Arjan Kortholt; expected completion 2022).

• Pien Goldsteen: Neuro-Chip: Neuronal control of human internal organ pathophysiology

(Co-supervision with Reinoud Gosens; expected completion 2021).

• Alejandro Marmolejo-Garza: The role of mitochondrial function in neurodegeneration

(Co-supervision with Erik Boddeke, expected completion 2024).

• Yuequ Zhang: Neuorprotective effects of novel SK channel modulators

• Nad'a Majernikova: Ferroptosis in Alzheimer's disease

(Co-supervision with Wilfred den Dunnen; expected completion 2024).

• Tingting Chen: Neuorprotective effects of extracellular mitochondria in neurodegeneration

(Co-supervision with Ulrich Eisel; expected completion 2025).

Alumni:

Dr. Inge Krabbendam: Impact of SK channel modulation on mitochondrial dysfunction and inflammation. (November 2020)

Dr. Angelica Sabogal: The cross-talk between mitochondrial metabolism and inflammation in neurodegeneration. (January 2020)

Dr. Birgit Honrath: Impact of alterations in mitochondrial calcium homeostasis on mitochondrial metabolism (December 2017).

Former Master projects supervised:

2016-2017: Jacob Slagter: Inhibition of immune-check points in Alzheimer`s disease.

2016-2017: Carmen IJsebaart: Calcium regulation at the interface between ER-mitochondrial contact points.

2015-2016: Tammo Meyer: The role of SK channel activation in mitochondrial metabolism and ROS production.

2015-2016: Valentina Pegoretti: Mitochondrial SK channel involvement in neuronal HT-22 cell oxidative stress.

2015-2016: Chairi Misrielal: The effects of diet and circadian rhythm on brain mitochondrial function.