http://www.sciencedirect.com/science/article/pii/S0301008213000099
Abstract
Chemokines – chemotactic cytokines – are small secreted proteins that attract and activate immune and non-immune cells in vitro and in vivo.
It has been suggested that chemokines and their receptors play a role
in the central nervous system (CNS), in addition to their well
established role in the immune system. We focus here on three
chemokines—CXCL12 (C-X-C motif ligand 12), CCL2 (C-C motif ligand 2),
and CX3CL1 (C-X-3C motif ligand 1) – and their principal receptors –
CXCR4 (C-X-C motif receptor 4), CCR2 (C-C motif receptor 2) and CX3CR1
(C-X-3C motif receptor 1), respectively. We first introduce the
classification of chemokines and their G-protein coupled receptors and
the main signaling pathways triggered by receptor activation. We then
discuss the cellular distribution of CXCL12/CXCR4, CCL2/CCR2 and
CX3CL1/CX3CR1 in adult brain and the neurotransmission and
neuromodulation effects controlled by these chemokines in the adult CNS.
Changes in the expression of CXCL12, CCL2 and CX3CL1 and their
respective receptors are also increasingly being implicated in the
pathogenesis of CNS disorders, such as Alzheimer's disease, Parkinson's
disease, HIV-associated encephalopathy, stroke and multiple sclerosis,
and are therefore plausible targets for future pharmacological
intervention. The final section thus discusses the role of these
chemokines in these pathophysiological states. In conclusion, the role
of these chemokines in cellular communication may make it possible: (i)
to identify new pathways of neuron–neuron, glia–glia or neuron–glia
communications relevant to both normal brain function and
neuroinflammatory and neurodegenerative diseases; (ii) to develop new
therapeutic approaches for currently untreatable brain diseases.
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