Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases

• Published in: Brain Research Reviews Vol. 48; no. 1; pp. 16 - 42
• Main Authors: Cartier, Laetitia, Hartley, Oliver, Dubois-Dauphin, Michel, Krause, Karl-Heinz
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01-02-2005; Elsevier
• Subjects: Animals; Biological and medical sciences; Brain; Cell Death - immunology; Central Nervous System - anatomy & histology; Central Nervous System - immunology; Central Nervous System - metabolism; Chemokine receptors; Chemokines; Chemokines - immunology; Chemokines - metabolism; Chemotaxis - immunology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Encephalitis - immunology; Encephalitis - metabolism; Human immunodeficiency virus; Humans; Inflammation; Medical sciences; Microglia - immunology; Microglia - metabolism; Neurodegenerative diseases; Neurodegenerative Diseases - immunology; Neurodegenerative Diseases - metabolism; Neurology; Neurons - immunology; Neurons - metabolism; Neurons - pathology; Receptors, Chemokine - immunology; Receptors, Chemokine - metabolism; Disorders of the nervous system; Brain; Inflammation; Neurodegenerative diseases; Chemokine receptors; Chemokines; Chemokine; Nervous system diseases; Central nervous system; Degenerative disease; Chemokine receptor; Review; Cerebral disorder
• ISSN: 0165-0173; 1872-6321
• DOI: 10.1016/j.brainresrev.2004.07.021

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.