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5-HT1A receptor agonist-mediated protection from MPTP toxicity in mouse and macaque models of Parkinson's disease

AuthorsBezard, Erwan; Gerlach, I.; Moratalla, Rosario CSIC ORCID ; Gross, C. E.; Jork, R.
Issue Date2006
PublisherAcademic Press
CitationNeurobiology of Disease 23: 77- 86 (2006)
AbstractExcitotoxicity-mediated cell death is involved in Parkinson's disease (PD). 5-HT1A receptor agonists can protect from such mechanisms. The current study demonstrates that the 5-HT1A agonists BAY 639044 and repinotan have neuroprotective effects in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. In addition, we also show that both compounds delay the appearance of parkinsonian motor abnormalities in a MPTP monkey model that recapitulates the progressive nature of PD. Thus, BAY 639044 or repinotan treatment was initiated when there was 30% neuronal death in the substantia nigra pars compacta, and nerve terminal loss in the striatum was 40%, i.e., compatible with the clinical situation where early symptomatic patients would receive such a treatment. The delay in appearance of parkinsonian motor abnormalities is a consequence of partial neuroprotection of nigrostriatal dopamine neurons, both at neuronal and terminal levels as shown for BAY 639044. These results suggest that 5-HT1A agonists, such as BAY 639044, may protect from neurodegeneration and delay the worsening of motor symptoms in Parkinson patients. © 2006.
Identifiersdoi: 10.1016/j.nbd.2006.02.003
issn: 0969-9961
Appears in Collections:(IC) Artículos
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