| Popis: |
Parkinson’s 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 marked increase in RANTES (regulated on activation, normal T cell expressed and secreted) 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 (MPTP)-intoxicated hemiparkinsonian monkeys. Since RANTES and eotaxin share a common receptor CCR5, we examined the efficacy of maraviroc, an inhibitor of CCR5 and an FDA-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 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. |
