Immunology & Inflammation: Interactions of amyloid-beta with the neurotrophin receptor p75ntr mediate dendritic spine alterations
Despite new therapeutic approaches, neurodegenerative diseases (NDs) like Alzheimer’s Disease (AD) cannot be treated sufficiently, mainly because of unknown origin. Peripheral infections and inflammations but especially neuroinflammatory processes in the brain are regarded as risk factors for the progression and probably also the onset of AD and other NDs. To find a treatment or at least to delay the onset of AD is of tremendous importance, since it is predicted that 2030 2.5 Mio people will be affected in Germany (worldwide more than 75 Mio). A cure will only be possible with a better understanding of the cause and the progression of the diseases as well as the identification of early biomarkers.
For many years, the CNS was regarded as immune privileged. Today, it is known that peripheral immune processes affect brain function and might influence the onset and the progression of NDs, like AD. Our research is focused on the hippocampus, the brain region responsible for learning and memory and early affected in AD.
In this project we characterize structural and functional consequences of different immune stimulation by using:
- bacterial cell wall components (HZI-DZNE Joint Project with M.Heneka),
- influenza infection with various non- and neurotropic viral subtypes (with K. Schughart, INFG HZI) or
- Toxoplasma gondii infection (cooperation I. Dunay, SFB 854, Magdeburg)
on neurons or as immune-challenge for animals to identify cellular mechanisms, which might result in new strategies to treat inflammatory diseases. In addition we try to elucidate possible signaling routes between the immune system and the nervous system. In particular the neurotrophin receptor p75NTR is of particular interest, since it serves as a receptor for soluble amyloid-β aggregates (Aβ) and might be involved in mediating synaptic dysfunction and loss during AD. We analyse the influence of infections and inflammations on the development and strength of AD. Moreover, we focus on the function of Type I Interferon Receptor (IFNAR), an innate immune system component mandatory for viral clearance in the brain, in immune and nervous system as the immune system components might have specific functions in neuronal processes (with U. Kalinke, EXPI; Twincore Hannover). The understanding of neuroinflammatory mechanisms and processes is of upmost importance to cure acute and chronic inflammatory brain diseases and to restrict extend of NDs.
- SFB 854
- INCURE (BMBF/EU)
- I&I (Helmholtz society)
- N-RENNT (Land Niedersachsen)