MPTP induces alpha-synuclein aggregation in the substantia... : NeuroReport (original) (raw)

CLINICAL NEUROSCIENCE AND NEUROPATHOLOGY

Kowall, Neil W.1,4; Hantraye, Philippe2; Brouillet, Emmanuel2; Beal, M Flint3; McKee, Ann C.1; Ferrante, Robert J.1

1Geriatric Research Education Clinical Center, Veterans Affairs Medical Center, Bedford, MA 01730, and the Departments of Neurology and Pathology, Boston University School of Medicine, USA

2Unité de Recherche Associé Commissariat á l'Energie Atomique, Centre National de la Recherche Scientifique 2210, Service Hospitalier Frederic, Joliot, Orsay, France

3Neurochemistry Laboratory, Neurology Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

4Corresponding Author: Neil W. Kowall

Acknowledgements: Thanks to David Clayton for the generous gift of α-synuclein antibody and to Karen Smith for expert technical assistance. This work was supported by the US Department of Veterans Affairs, US Department of Defense, American Parkinson's Disease Association and by the National Institutes of Health (AG13846, NS37102, NS16367 and NS31579).

Received 13 October 1999; accepted 3 November 1999

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.