Project Details
Projekt
KFO 177: Innate Immunity in Chronic Neurodegeneration
Subject Area
Medicine
Term
from 2007 to 2013
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 33995431
An early and strong innate immune reaction is a common feature of a variety of chronic disorders of the central nervous system (CNS) including Multiple sclerosis (MS) and Alzheimer´s disease (AD). At the same time, both disorders are characterised by early axonal and synaptic dysfunction and injury - deleterious events that are thought to underlie the irreversible clinical deficits in both diseases. At present, the exact pathomechanism of early neuronal damage is not completely understood. However, activated microglia as the major cellular mediator of the innate immune response is known to be associated with neuronal damage and may have a causative role in both MS and AD. In this Clinical Research Unit, the mechanism of innate inflammatory reactions will be studied in cellular and animal models of MS and AD hypothesising that proinflammatory mediators of activated microglia and other immune cells invading the CNS strongly contribute to the pathogenesis of these diseases and are involved in chronic neurodegeneration.
Both diseases have been intentionally combined in order to transfer the knowledge collected in the primary neurodegeneration of AD to the new observation that axonal degeneration is occurring early in MS. Vice versa, insights into the inflammatory response gained in MS can be fruitfully applied to understand the recently recognised innate immune response in AD. Thus, the major research goals of the Clinical Research Unit are
(1) to identify the molecular mechanisms of innate immunity in cell culture and animal models of MS and AD,
(2) to study the involvement of innate immunity in axonal and synaptic damage of MS and AD and
(3) to modulate and target the innate brain immunity in order to restrict detrimental and to promote beneficial effects.
Both diseases have been intentionally combined in order to transfer the knowledge collected in the primary neurodegeneration of AD to the new observation that axonal degeneration is occurring early in MS. Vice versa, insights into the inflammatory response gained in MS can be fruitfully applied to understand the recently recognised innate immune response in AD. Thus, the major research goals of the Clinical Research Unit are
(1) to identify the molecular mechanisms of innate immunity in cell culture and animal models of MS and AD,
(2) to study the involvement of innate immunity in axonal and synaptic damage of MS and AD and
(3) to modulate and target the innate brain immunity in order to restrict detrimental and to promote beneficial effects.
DFG Programme
Clinical Research Units
Projects
- Common resources of the Clinical Research Group (Applicant Heneka, Michael Thomas )
- Human-specific microglial receptor Siglec-11 in neuroinflammatory diseases (Applicant Neumann, Harald )
- Immune biomarker- and microRNA-guided dose escalation phase I clinical study of a RIG-Iigand for the treatment of multiple sclerosis (Applicant Hartmann, Gunther )
- Inflammasome activiation in Alzheimer´s disease (Applicant Latz, Eicke )
- Local control of inflammation neuronal damage by Peroxisome-profilator-activated receptory (PPARy) in EAE (Applicant Klotz, Luisa )
- Mechanisms of microglia-mediated neuronal damage and dysfunction: Role of the "TNFa-Zn2+" cascade (Applicant Beck, Heinz )
- Modulation of neurodegeneration and neuroinflamation by the liver X receptor (LXR) in Alzheimer`s disease (Applicant Heneka, Michael Thomas )
- Role of the microglial chemokine receptor CX3CR1 in Alzheimer´s disease (Applicant Fuhrmann, Martin )
- The role of the CXCR3 chemokine system in Alzheimer´s disease (AD) (Applicant Müller, Marcus )
- y-Secretase-dependent processes in microglial functions (Applicant Walter, Ph.D., Jochen )
Spokesperson
Professor Dr. Thomas Klockgether
