Chemokines/chemokine receptors in the central nervous system and Alzheimer's disease.
Alzheimer's disease (AD) is the most common cause of dementia in the elderly, and the fourth leading cause of death in the United States. Its pathological changes include amyloid beta deposits, neurofibrillary tangles and a variety of 'inflammatory' phenomenon such as activation of microglia and astrocytes. The pathological significance of inflammatory responses elicited by resident central nervous system (CNS) cells has drawn considerable attention in recent years. Chemokines belongs to a rapidly expanding family of cytokines, the primary function of which is control of the correct positioning of cells in tissues and recruitment of leukocytes to the site of inflammation. Study of this very important class of inflammatory cytokines may greatly help our understanding of inflammation in the progress of AD, as well as other neurodegenerative diseases. So far, immunoreactivity for a number of chemokines (including IL-8, IP-10, MIP-1beta, MIPalpha and MCP-1) and chemokine receptors (including CXCR2, CXCR3, CXCR4, CCR3, CCR5 and Duffy antigen) have been demonstrated in resident cells of the CNS, and upregulation of some of the chemokines and receptors are found associated with AD pathological changes. In this review, we summarize findings regarding the expression of chemokines and their receptors by CNS cells under physiological and pathological conditions. Although little is known about the potential pathophysiological roles of chemokines in CNS, we have put forward hypotheses on how chemokines may be involved in AD.
Xia
M Q
MQ
Alzheimer's Research, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 02114, USA.
Hyman
B T
BT
D000544:Alzheimer Disease / Q000209:etiology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism / Q000502:physiology*; D002633:Chemotaxis; D006801:Humans; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism*; D012377:Rodentia
D016229:Amyloid beta-Peptides; D018925:Chemokines; D019707:Receptors, Chemokine