Abstract
Parkin and alpha-synuclein are two proteins that are associated with the pathophysiology of Parkinson's disease (PD). Parkin is present in Lewy bodies and axonal spheroids in brains affected by PD, and mutations in parkin cause hereditary forms of Parkinsonism. Alpha-synuclein is a major component of Lewy bodies and is associated with rare cases of PD. We now show that parkin binds to alpha-synuclein, including conditions associated with alpha-synuclein aggregation. Parkin and alpha-synuclein complexes were observed in BE-M17 cells under basal conditions, in BE- M17 cells under oxidative conditions and in brains from control or PD donors. Double staining of PD brains shows parkin and alpha-synuclein co-localize to the same pathological structures (both Lewy bodies and axonal spheroids). These results suggest that parkin interacts with alpha-synuclein and could contribute to the pathophysiology of PD more generally than was previously considered.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aged
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Antibodies
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Axons / metabolism*
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Axons / pathology
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Binding Sites / physiology
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Brain / metabolism*
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Brain / pathology
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Brain / physiopathology
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Dopamine / pharmacology
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Ferrous Compounds / pharmacology
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Humans
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Immunohistochemistry
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Lewy Bodies / metabolism*
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Lewy Bodies / pathology
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Ligases / metabolism*
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Nerve Tissue Proteins / metabolism*
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Nerve Tissue Proteins / pharmacokinetics
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Oxidative Stress / drug effects
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Oxidative Stress / physiology
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Parkinson Disease / metabolism*
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Parkinson Disease / pathology
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Parkinson Disease / physiopathology
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Precipitin Tests
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Synucleins
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / metabolism
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Tumor Cells, Cultured / pathology
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Ubiquitin-Protein Ligases*
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alpha-Synuclein
Substances
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Antibodies
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Ferrous Compounds
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Nerve Tissue Proteins
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SNCA protein, human
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Synucleins
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alpha-Synuclein
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Ubiquitin-Protein Ligases
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parkin protein
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Ligases
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ferrous chloride
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Dopamine