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Low-Dose Maraviroc, an Antiretroviral Drug, Attenuates the Infiltration of T Cells into the Central Nervous System and Protects the Nigrostriatum in Hemiparkinsonian Monkeys.
J Immunol 2019JI

Abstract

Parkinson disease (PD) is the most common neurodegenerative movement disorder in humans. Despite intense investigation, no effective therapy is available to stop the progression of this disease. It is becoming clear that both innate and adaptive immune responses are active in PD. Accordingly, we have reported a marked increase in RANTES and eotaxin, chemokines that are involved in T cell trafficking, in vivo in the substantia nigra (SN) and the serum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-intoxicated hemiparkinsonian monkeys. Because RANTES and eotaxin share a common receptor, CCR5, we examined the efficacy of maraviroc, an inhibitor of CCR5 and a Food and Drug Administration-approved drug against HIV infection, in hemiparkinsonian rhesus monkeys. First, we found glial limitans injury, loss of GFAP immunostaining, and infiltration of T cells across the endothelial monolayer in SN of hemiparkinsonian monkeys. However, oral administration of a low dose of maraviroc protected glia limitans partially, maintained the integrity of endothelial monolayer, reduced the infiltration of T cells, attenuated neuroinflammation, and decreased α-synucleinopathy in the SN. Accordingly, maraviroc treatment also protected both the nigrostriatal axis and neurotransmitters and improved motor functions in hemiparkinsonian monkeys. These results suggest that low-dose maraviroc and other CCR5 antagonists may be helpful for PD patients.

Authors+Show Affiliations

Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612.Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612.Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612.Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612.Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612.Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612 kalipada_pahan@rush.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31043478

Citation

Mondal, Susanta, et al. "Low-Dose Maraviroc, an Antiretroviral Drug, Attenuates the Infiltration of T Cells Into the Central Nervous System and Protects the Nigrostriatum in Hemiparkinsonian Monkeys." Journal of Immunology (Baltimore, Md. : 1950), 2019.
Mondal S, Rangasamy SB, Roy A, et al. Low-Dose Maraviroc, an Antiretroviral Drug, Attenuates the Infiltration of T Cells into the Central Nervous System and Protects the Nigrostriatum in Hemiparkinsonian Monkeys. J Immunol. 2019.
Mondal, S., Rangasamy, S. B., Roy, A., Dasarathy, S., Kordower, J. H., & Pahan, K. (2019). Low-Dose Maraviroc, an Antiretroviral Drug, Attenuates the Infiltration of T Cells into the Central Nervous System and Protects the Nigrostriatum in Hemiparkinsonian Monkeys. Journal of Immunology (Baltimore, Md. : 1950), doi:10.4049/jimmunol.1800587.
Mondal S, et al. Low-Dose Maraviroc, an Antiretroviral Drug, Attenuates the Infiltration of T Cells Into the Central Nervous System and Protects the Nigrostriatum in Hemiparkinsonian Monkeys. J Immunol. 2019 May 1; PubMed PMID: 31043478.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Low-Dose Maraviroc, an Antiretroviral Drug, Attenuates the Infiltration of T Cells into the Central Nervous System and Protects the Nigrostriatum in Hemiparkinsonian Monkeys. AU - Mondal,Susanta, AU - Rangasamy,Suresh B, AU - Roy,Avik, AU - Dasarathy,Sridevi, AU - Kordower,Jeffrey H, AU - Pahan,Kalipada, Y1 - 2019/05/01/ PY - 2018/04/24/received PY - 2019/04/05/accepted PY - 2020/11/01/pmc-release PY - 2019/5/3/entrez PY - 2019/5/3/pubmed PY - 2019/5/3/medline JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. N2 - Parkinson disease (PD) is the most common neurodegenerative movement disorder in humans. Despite intense investigation, no effective therapy is available to stop the progression of this disease. It is becoming clear that both innate and adaptive immune responses are active in PD. Accordingly, we have reported a marked increase in RANTES and eotaxin, chemokines that are involved in T cell trafficking, in vivo in the substantia nigra (SN) and the serum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-intoxicated hemiparkinsonian monkeys. Because RANTES and eotaxin share a common receptor, CCR5, we examined the efficacy of maraviroc, an inhibitor of CCR5 and a Food and Drug Administration-approved drug against HIV infection, in hemiparkinsonian rhesus monkeys. First, we found glial limitans injury, loss of GFAP immunostaining, and infiltration of T cells across the endothelial monolayer in SN of hemiparkinsonian monkeys. However, oral administration of a low dose of maraviroc protected glia limitans partially, maintained the integrity of endothelial monolayer, reduced the infiltration of T cells, attenuated neuroinflammation, and decreased α-synucleinopathy in the SN. Accordingly, maraviroc treatment also protected both the nigrostriatal axis and neurotransmitters and improved motor functions in hemiparkinsonian monkeys. These results suggest that low-dose maraviroc and other CCR5 antagonists may be helpful for PD patients. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/31043478/Low-Dose_Maraviroc,_an_Antiretroviral_Drug,_Attenuates_the_Infiltration_of_T_Cells_into_the_Central_Nervous_System_and_Protects_the_Nigrostriatum_in_Hemiparkinsonian_Monkeys L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=31043478 DB - PRIME DP - Unbound Medicine ER -