Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases.
Chemokines were originally described as chemotactic cytokines involved in leukocyte trafficking. Research over the last decade, however, has shown that chemokine receptors are not restricted to leukocytes. In the brain, chemokine receptors are not only found in microglia (a brain macrophage), but also in astrocytes, oligodendrocytes and neurons. In this review, we describe the spatial and cellular distribution of chemokine receptors in the brain, distinguishing between constitutively and inducibly expressed receptors. We then discuss possible physiological functions, including neuronal migration, cell proliferation and synaptic activity. Evidence is emerging that chemokine receptors are also involved in neuronal death and hence neurodegenerative diseases. Chemokines may induce neuronal death either indirectly (e.g. through activation of microglia killing mechanisms) or directly through activation of neuronal chemokine receptors. Disease processes in which chemokines and their receptors are likely to be involved include multiple sclerosis (MS), Alzheimer's disease (AD), HIV-associated dementia (HAD) and cerebral ischemic disease. The study of chemokines and their receptors in the central nervous system (CNS) is not only relevant for the understanding of brain physiology and pathophysiology, but may also lead to the development of targeted treatments for neurodegenerative diseases.
Cartier
Laetitia
L
Biology of Ageing Laboratory, Department of Geriatrics, Geneva University Hospitals, 2 chemin du Petit-Bel Air, CH-1225 Chêne-Bourg, Switzerland.
Hartley
Oliver
O
Dubois-Dauphin
Michel
M
Krause
Karl-Heinz
KH
D000818:Animals; D016923:Cell Death / Q000276:immunology; D002490:Central Nervous System / Q000033:anatomy & histology / Q000276:immunology* / Q000378:metabolism; D018925:Chemokines / Q000276:immunology* / Q000378:metabolism; D002633:Chemotaxis / Q000276:immunology; D004660:Encephalitis / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000276:immunology* / Q000378:metabolism; D009474:Neurons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019707:Receptors, Chemokine / Q000276:immunology* / Q000378:metabolism
D018925:Chemokines; D019707:Receptors, Chemokine