MPTP induces alpha-synuclein aggregation in the substantia nigra of baboons.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity reproduces many of the features of Parkinson's disease (PD). alpha-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 alpha-synuclein antibody to define the relationship between neuronal degeneration and alpha-synuclein immunoreactivity in the substantia nigra. MPTP-induced neuronal degeneration was associated with the redistribution of alpha-synuclein from its normal synaptic location to aggregates in degenerating neuronal cell bodies. alpha-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.
Kowall
N W
NW
Geriatric Research Education Clinical Center, Veterans Affairs Medical Center, Bedford, MA 01730, USA.
Hantraye
P
P
Brouillet
E
E
Beal
M F
MF
McKee
A C
AC
Ferrante
R J
RJ
D000818:Animals; D015259:Dopamine Agents / Q000633:toxicity*; D005911:Gliosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000473:pathology; D020267:MPTP Poisoning / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010215:Papio; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D020955:Striatonigral Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology; D051843:Synucleins; D051844:alpha-Synuclein
D015259:Dopamine Agents; D009419:Nerve Tissue Proteins; D051843:Synucleins; D051844:alpha-Synuclein