Project Details
Projekt
T cells as modulators of microglia-mediated neurodegeneration in Niemann Pick type C (NPC) disease
Applicants
Professor Dr. Arthur Liesz; Sabina Tahirovic, Ph.D.
Subject Area
Experimental Models for the Understanding of Nervous System Diseases
Molecular Biology and Physiology of Neurons and Glial Cells
Molecular and Cellular Neurology and Neuropathology
Molecular Biology and Physiology of Neurons and Glial Cells
Molecular and Cellular Neurology and Neuropathology
Term
since 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 500118375
The aim of our project is to study microglia-T cell interaction in the context of neurodegeneration and neuroinflammation. We will use our newly generated rodent Niemann-Pick type C (NPC) model recapitulating microglia-mediated neurodegeneration. NPC is a rare progressive autosomal recessive lipid storage disorder largely caused by mutations in NPC1 gene that controls intracellular lipid homeostasis. It presents with complex visceral, neurological, and psychiatric symptoms that most often manifest at childhood age and rapidly progress to neurodegeneration and pre-mature death. There is currently no cure for this devastating form of childhood dementia. Neuroinflammation is one of the key pathological hallmarks that occurs prior to neurodegeneration. To determine the potential of the adaptive immune system to contribute to neuroinflammation and neurodegeneration, we will explore the myeloid-specific NPC1 depletion mouse model. We aim at (i) characterizing T cell recruitment and phenotypes in NPC pathology, (ii) determining the functional role of T cells on microglial phenotypes and NPC pathology, (iii) testing microglia as mediators of T cell effects and (iv) validating T cell-microglia interactions in human NPC brain tissue and blood. With the results of the 4 work packages we expect to identify a role of the adaptive immune system in neurodegeneration and contribute to better evaluate its potential for therapeutic modulation.
DFG Programme
Priority Programmes
