MPTP induces alpha-synuclein aggregation in the substantia nigra of baboons

Abstract

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity reproduces many of the features of Parkinson's disease (PD). α-Synuclein has been identified as a prominent component of the Lewy body (LB), the pathological hallmark of PD. MPTP-treated primates have been reported to develop intraneuronal inclusions but not true Lewy bodies. We administered MPTP to baboons and used a monoclonal α-synuclein antibody to define the relationship between neuronal degeneration and α-synuclein immunoreactivity in the substantia nigra. MPTP-induced neuronal degeneration was associated with the redistribution of α-synuclein from its normal synaptic location to aggregates in degenerating neuronal cell bodies. α-Synuclein aggregation induced by MPTP models the early stages of Lewy body formation and may be a fundamental step in the evolution of neuronal degeneration in PD.