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H2020Individual fellowship2017–2019

INFLAMM-ALZ · The Role of Neuroinflammation in Alzheimer’s Disease

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2017-11-01 → 2019-10-31
EU contribution
€173,857
Participants
1
Scheme
MSCA-IF

Lines connect the coordinator with its partners.

Results in brief

The Role of Neuroinflammation in Alzheimer’s Disease

Alzheimer’s disease (AD) is a major public health problem with substantial economic and social impacts around the world. With the development of diagnostic methods future patients can potentially be identified decades before they exhibit any symptoms. This makes it possible to treat future AD patients earlier, if curative treatments were available. However, we are still lacking therapies for AD that can prevent or attenuate the disease progress. The classical neuropathological hallmarks of AD include aggregation of amyloid β (Aβ) peptides into plaques in the brain, as well as the presence of neurofibrillary tangles composed of hyperphosphorylated tau protein. However, increasing evidence suggests that brain-specific macrophages, i.e. microglia, play a critical role in the pathogenesis of AD. The microglial cells are thought to be both protecting as well as mediators of neurodegeneration in AD. Being able to phagocytose and degrade toxic proteins, they might prevent the aggregation of Aβ plaques, but when activated, they could lead to ongoing, chronic inflammatory events contributing to the degradation of the brain. To be able to make use of the inflammatory system and microglia for the development of future AD therapeutics, we need to increase our understanding of the normal and pathological functions of these cells. The main project objective was to provide an in-depth understanding of how microglia contribute to the pathogenesis of AD, with focus on Aβ toxicity, memory impairment and microglia function. This project is a large interdisciplinary collaborative effort involving well-established methods such as confocal imaging and transgenic zebrafish, with newly developed photopharmacological tools.

Data: CORDIS, © European Union

Project objective

Alzheimer’s disease (AD) is a major public health problem with substantial economical and social impacts worldwide. Despite intense research, the pathological mechanisms of AD are still unclear. Under homeostasis, a delicate balance is struck between disposal of pathogenic proteins by the brain’s immune cells, microglia, and the inflammation produced by these cells. Indeed, during an acute activation, microglia are protective, but if microglia enter an over-activated state they can induce chronic inflammation through oxidative stress that in turn leads to neuronal damage. Thus, gaining data on the chain of events involved in microglial action is a prerequisite to understanding AD. This project is a large interdisciplinary collaborative effort involving well-established methods such as confocal imaging and transgenic zebrafish, with newly developed photopharmacological tools. Drs Kettunen, Grøtli and Andréasson provide the world-leading expertise required for the project. By coordinating this project, Dr Mourabit will gain invaluable experience in biomedical research, photochemistry, project management, supervision, and the production of scientific results. The novel photoresponsive probes used here will allow for photonic in vivo de/activation of microglia, generating new information on their spatiotemporal activity, in real-time. This state-of-the-art resolution of cell-tracking and control of microglial signalling will provide innovative data on the pathology of neuroinflammation. We believe this interdisciplinary team will push the boundaries of research in AD. This project has the potential to identify new treatments for AD, and influence the direction of neurobiology. This project will create a unique career opportunity for Dr Mourabit, enabling him to crossover from an environmental background to biomedical research. The marrying of such interconnected disciplines will help Dr Mourabit set the foundations of an eclectic and vibrant research group.

Original text from CORDIS.

Participants

  • GOETEBORGS UNIVERSITET · GoeteborgCoordinatorSweden

Links

Data: CORDIS, © European Union