A new perspective on brain diseases

Prof. Magdalena Dziembowska with collaborators
Dr Anna Malik with collaborators

The brain’s function depends on the harmonious cooperation of neurons and glial cells. Disruptions in their functioning can contribute to the development of serious conditions such as glioma or autism spectrum disorder (ASD). Research conducted at the Faculty of Biology UW helps to understand the molecular mechanisms behind these diseases and opens the path to new therapies.

One research team is investigating the molecular basis of synaptic plasticity, whose disruptions are observed in neurodevelopmental diseases like ASD. Scientists have discovered a mutation in the TRAP1 gene in ASD patients, which disrupts mitochondrial and synaptic function in the brain. In a mouse model, a reduced number of synaptic mitochondria and metabolic disturbances were identified, suggesting a role for mitochondria in the etiology of autism spectrum disorder. These findings could contribute to the development of more effective therapies.

Another research team focuses on the response of glial cells, including microglia, in brain disorders such as glioblastoma multiforme. Glioblastoma, an aggressive cancer, reprograms microglia to support tumor development rather than fight it. Scientists have identified the protein SorLA as a key regulator of microglial activity. Removal of SorLA in a mouse model unlocked the anti-tumor properties of microglia, leading to tumor growth inhibition.

MODERN APPLICATIONS:

Research on mitochondria and microglia could contribute to the development of therapies targeting neurological disorders, improving treatment effectiveness and the quality of life for patients.

FIGURE CAPTIONS:

Top: A section of a mouse brain, including the hippocampus, marked with neuron markers (NeuN, green), activated astrocytes (GFAP, red), and cell nuclei (DAPI, blue). The sample is from a transgenic mouse model of Alzheimer’s disease, showing astrocyte activation.

Bottom: 1. A section of a mouse brain, including the cortex, marked with microglial marker (Iba1, green) and SorLA protein (red), along with cell nuclei (DAPI, blue). 2. A mouse neuron in a brain section. 3. A section of a mouse brain after ischemic stroke (MCAo model), marked with microglial markers (Iba1, green), activated astrocytes (GFAP, red), and cell nuclei (DAPI, blue). 4. A section of a mouse brain with glioma, marked with tumor cells (red), microglia (Tmem119, green), and cell nuclei (DAPI, blue).

RELATED PUBLICATIONS:

Dr Anna Malik’s group

1. Kaminska P, Tempes A, Scholz E, Malik AR (2024) Cytokines on the way to secretion. Cytokine Growth Factor Rev 79:52-65. doi: 1016/j.cytogfr.2024.08.003
2. Kaminska P et al. (2024) SorLA restricts TNFα release from microglia to shape a glioma-supportive brain microenvironment. EMBO Rep 25:2278-2305. doi: 1038/s44319-024-00117-6

RELATED PROJECTS:

1. VPS10P domain receptors in phenotypic polarization of astrocytes and microglia in the diseased brain– Opus grant, National Science Centre (NCN), 2021-2025, PI: A. Malik
2. Molecular background of civilization diseases affecting the brain: focus on VPS10P domain receptors in phenotypic polarization of glia – Action I.3.4 of the Excellence Innitiative – Research University (IDUB) Programme, 2022-2024, PI: A. Malik