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Re-circulating Phagocytes Loaded with CNS Debris: A Potential Marker of Neurodegeneration in Parkinsons Disease?

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Special Issues: Biofluid Biomarkers for Parkinson’s Disease

Diagnosis and monitoring of diseases by measurement of biochemical markers has most commonly been performed on samples of peripheral blood. However, no such markers are available for clinical use in the major diseases of the central nervous system (CNS). In Parkinson's disease circulating biomarkers would find clinical utility in early diagnosis and also monitoring of disease progression. Of particular interest is early diagnosis as this would create .a window of opportunity for treatment with neuroprotective drugs. We have developed a novel strategy for monitoring disease activity in the CNS based on the recognition that tissue injuries incite inflammation and recruitment of phagocytes that engulf debris. We postulated that some of these debris laden phagocytes may return to the peripheral blood and their cargo of CNS proteins could be measured. If CNS antigens can be measured in PBMCs it may be an indicator of active neurodegeneration as the debris engulfed by phagocytes is completely degraded within days. To make this approach more specific to Parkinson's disease we probed PBMC lysates for neuromelanin as a marker of degeneration within the substancia nigra. We performed a proof of principle study in ten subjects with early PD and ten age and sex matched controls. The biomarkers neuromelanin, Tau protein, UCH-L1 and HPCAL-1 were measured in PBMC lysates from these two groups. Neuromelanin and Tau protein mean levels were elevated in PD compared with controls and was extremely statistically significant in both cases. UCH-L1 and HPCAL-1 mean levels were elevated in PD over controls and were not quite significant in both cases. These results suggest that this is a promising new approach for diagnosis and monitoring of PD and potentially other CNS diseases.
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1. Berg D, Marek K, Ross GW, Poewe W (2012). Defining At-Risk Populations for Parkinson's disease: Lessons from Ongoing Studies. Movement Disord 27: 656-665.    

2. Spiegel J, Storch A, Jost WH (2006). Early diagnosis of Parkinson's disease. J Neurol 253 Suppl4(S4): IV2-7.

3. Shi C, Pamer EG (2011). Monocyte recruitment during infection and inflammation. Nat Rev Immunol 11: 762-774.    

4. van der Goes A, Boorsmaa W, Hoekstraa K, et al. (2005). Determination of the sequential degradation of myelin proteins by macrophages. J Neuroimmunol 161: 12-20.    

5. Hoehn M, Yahr M (1967). Parkinsonism: onset, progression and mortality. Neurology 17: 427-42.    

6. Rosas AL, Nosanchuk JD, Casadevall (2001) Passive Immunization with Melanin-Binding Monoclonal Antibodies Prolongs Survival of Mice with Lethal Cryptococcus neoformans Infection. Infect Immun 69: 3410-3412.    

7. Dadachova E, Moadel T, Schweitzer AD, et al. (2006) Radiolabeled Melanin-Binding Peptides Are Safe and Effective in Treatment of Human Pigmented Melanoma in a Mouse Model of Disease. Cancer Biother Radio 21: 117-129.    

8. Lee V M-Y, Goedert M, Trojanowski JQ (2001) Neurodegenerative Tauopathies. Annu Rev Neurosci 24: 1121-1159.    

9. Burgoyne RD (2007). Neuronal Calcium Sensor Proteins: Generating Diversity in Neuronal Ca2+Signalling. Nat Rev Neurosci 8: 182-193

10. Doran JF, Jackson P, Kynoch PA, et al. (1983). Isolation of PGP 9. 5, a new human neurone-specific protein detected by high-resolution two-dimensional electrophoresis. J Neurochem 40: 1542-1547

11. Maraganore DM, Lesnick TG, Elbaz A, et al. (2004). UCHL1 is a Parkinson's disease susceptibility gene. Ann Neurol 55: 512-21.    

12. Leroy E, Boyer R, Auburger G, et al. (1998). The ubiquitin pathway in Parkinson's disease. Nature 395: 451-2.    

13. Harhangi BS, Farrer MJ, Lincoln S, etal. (1999). The Ile93Met mutation in the ubiquitin carboxy-terminal-hydrolase-L1 gene is not observed in European cases with familial Parkinson's disease. Neurosci Lett 270: 1-4.    

14. Joly S, Francke M, Ulbricht E, Beck S, et al. (2009) Cooperative Phagocytes: Resident Microglia and Bone Marrow Immigrants Remove Dead Photoreceptors in Retinal Lesions. Am J Pathol 174:2310-2323.    

15. Peng T, Li C, Li X, et al. (2014). Correlation between Serum RANTES Levels and the Severity of Parkinson's Disease. Oxid Med Cell Longev 2014: 1-4.

16. Scalzo P, Silva de Miranda A, Guerra Amaral DC et al. (2011). Serum levels of chemokines in Parkinson's disease. Neuroimmunomodulat 23: 240-4

Copyright Info: © 2015, Ramesh C. Nayak, et al., licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

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