NDLI: CXCR4 and CXCL12 Expression is Increased in the Nigro-Striatal System of Parkinson’s Disease

Content Provider	Springer Nature Link
Author	Shimoji, Mika Pagan, Fernando Healton, Edward B. Mocchetti, Italo
Copyright Year	2009
Abstract	Except for a handful of inherited cases related to known gene defects, Parkinson’s disease (PD) is a sporadic neurodegenerative disease of unknown etiology. There is increasing evidence that inflammation and proliferation of microglia may contribute to the neuronal damage seen in the nigro-striatal dopaminergic system of PD patients. Microglia events that participate in neuronal injury include the release of pro-inflammatory and neurotoxic factors. Characterizing these factors may help to prevent the exacerbation of PD symptoms or to remediate the disease progression. In rodents, the nigro-striatal system exhibits high expression of the chemokine receptor CXCR4. Its natural ligand CXCL12 can promote neuronal apoptosis. Therefore, the present study investigated the expression of CXCR4 and CXCL12 in post-mortem brains of PD and control (non-PD) individuals and in an animal model of PD. In the human substantia nigra (SN), CXCR4 immunoreactivity was high in dopaminergic neurons. Interestingly, the SN of PD subjects exhibited higher expression of CXCR4 expression and CXCL12 than control subjects despite the loss of dopamine (DA) neurons. This effect was accompanied by an increase in activated microglia. However, results from post-mortem brains may not provide indication as to whether CXCL12/CXCR4 can cause the degeneration of DA neurons. To examine the role of these chemokines, we determined the levels of CXCL12 and CXCR4 in the SN of MPTP-treated mice. MPTP produced a time-dependent up-regulation of CXCR4 that preceded the loss of DA neurons. These results suggest that CXCL12/CXCR4 may participate in the etiology of PD and indicate a new possible target molecule for PD.
Starting Page	318
Ending Page	328
Page Count	11
File Format	PDF
ISSN	10298428
Journal	Neurotoxicity Research
Volume Number	16
Issue Number	3
e-ISSN	14763524
Language	English
Publisher	Springer-Verlag
Publisher Date	2009-06-24
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Chemokines CXCL12/SDF-1α Dopamine neurons Human brains CCL5/RANTES MPTP Substantia nigra Striatum Microglia Neurobiology Pharmacology/Toxicology Neurochemistry Neurology Pharmaceutical Sciences/Technology Neurosciences
Content Type	Text
Resource Type	Article
Subject	Neuroscience Toxicology

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