The many roles of chemokine receptors in neurodegenerative disorders: emerging new therapeutical strategies.
Chemokines and chemokine receptors, primarily found to play a role in leukocyte migration to the inflammatory sites or to second lymphoid organs, have recently been found expressed on the resident cells of the central nervous system (CNS). These proteins are important for the development of the CNS and are involved in normal brain functions such as synaptic transmission. Increasing lines of evidence have implicated an involvement for chemokines and their receptors in several neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), human immunodeficiency virus-associated dementia (HAD), multiple sclerosis (MS), and stroke. Specific inhibition of the biological activities of chemokine receptors could gain therapeutic benefit for these neurodegenerative disorders. In recent years, non-peptide antagonists of chemokine receptors have been disclosed and tested in relevant pharmacological models and some of these inhibitors have entered clinical trials. The aim of this review is to outline the recent progress regarding the role of chemokines and their receptors in neurodegenerative diseases and the advancements in the development of chemokine receptor inhibitors as potential therapeutic approaches for these neurodegenerative diseases.
Mines
Marjelo
M
Department of Veterans Affairs and the Department of Biomedical Sciences, Division of Neurobiology and Neurotoxicology, Meharry Medical College, Nashville, TN 37208, USA.
Ding
Yun
Y
Fan
Guo-Huang
GH
D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D005786:Gene Expression Regulation; D006678:HIV / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008956:Models, Chemical; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000473:pathology*; D010300:Parkinson Disease / Q000188:drug therapy / Q000473:pathology; D019707:Receptors, Chemokine / Q000378:metabolism / Q000502:physiology*; D020521:Stroke / Q000188:drug therapy / Q000473:pathology; D016896:Treatment Outcome
D018925:Chemokines; D019707:Receptors, Chemokine