Complex role of chemokine mediators in animal models of Alzheimer's Disease

Abstract

Chemokines are a family of cytokines, first described to play a role in the immune system. However, neurons and glial cells also express chemokines and their receptors. In the central nervous system, chemokines are involved in several neural functions, in particular in the control of cell communications and neuronal activity. In pathological conditions, chemokines participate in neuroinflammatory and neurodegenerative processes. In Alzheimer's disease (AD), chemokines play a role in the development of the two main lesions, amyloid β plaques and neurofibrillary tangles. In addition, they contribute to the inflammatory response by recruiting T cells and controlling microglia/macrophages activation. Actually, targeting inflammatory pathways seems a promising therapeutic approach for the treatment of AD patients. This review summarizes our current knowledge on the roles of chemokines in AD animal models and the underlying mechanisms in which they take part. Better knowledge of the role of chemokines and their cellular receptors in AD could open new therapeutic perspectives.

Keywords: Alzheimer's disease; Animal model; Chemokine; Inflammation.

Fig. 1

Roles of chemokines in AD disease. Lack of CX3CR1/CX3CL1 interaction induces the release of IL-1β that binds to IL-1 receptor and leads to hyperphosphorylation of Tau but also to phagocytosis of Aβ peptides. Aβ peptides induce CXCL10 release from glial cells; its binding to CXCR3 may in turn inhibit microglial phagocytosis. CCR2-expressing perivascular macrophages contribute to clearance/transport of Aβ peptides outside the brain. CCR3 activation by CCL11 contributes to the formation of AD lesions via Tau phosphorylation and production of Aβ peptides. CXCR2 activation also mediates the release of Aβ peptides. CCR5/CCL3 overexpression induces the recruitment of peripheral T cells and participates to neuronal damages.