 |
New Scholar Award in Aging
|
Kathryn J.
Moore,
Ph.D.
Massachusetts General Hospital
|
Genetic and Functional Analysis of CD36-signaling in Age-related Chronic Inflammatory Diseases
In Alzheimer’s disease, a chronic inflammatory response to b-amyloid has been proposed to underly neuro-degenerative pathology. Central to this hypothesis is the observation that microglia are recruited to, and accumulate at, sites of b-amyloid deposition. These cells produce inflammatory mediators capable of inciting chronic inflammation and tissue damage, including interleukin-1b, tumor necrosis factor-a and monocyte chemo-attractant protein-1, which have been detected in the sera of Alzheimer’s patients. The identification of a microglial receptor-mediated signaling pathway that initiates this inflammatory response to b-amyloid and strategies to interrupt this signaling, could contribute substantially to the development of novel approaches to treat Alzheimer’s disease.
CD36 is a pattern recognition receptor present on macrophages, including brain microglia, that performs innate immune surveillance. We have recently identified a CD36-dependent signaling cascade activated by b-amyloid, that regulates the production of microglial pro-inflammatory mediators in vitro and promotes the recruitment of microglia in vivo. We hypothesize that targeted interruption of this CD36 signaling cascade would abrogate microglial recruitment and activation to b-amyloid, and that this in turn would inhibit the chronic inflammation and tissue damage surrounding senile plaques. Our research effort is directed at understanding how CD36 initiates cellular signaling and developing strategies to interrupt these events. If blocking CD36 signaling inhibits Alzheimer’s disease pathology, this would identify a target for the development of therapeutic agents to treat Alzheimer’s disease and another chronic inflammatory disease involving CD36 that is associated with aging, atherosclerosis
Contact
Dr. Moore.
|
|
