Parkinson's disease alpha-synuclein mutations exhibit defective axonal transport in cultured neurons
| Autor: | Christopher C.J. Miller, Ayodeji A. Asuni, Andrew J. Grierson, Diane P. Hanger, Michelle A. Utton, Alun M. Davies, Steven Ackerley, Brian H. Anderton, Vladimir L. Buchman, Josephine E. Hill, Anirban R. Saha |
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| Rok vydání: | 2004 |
| Předmět: |
Parkinson's disease
DNA Complementary animal diseases Synucleins Nerve Tissue Proteins Biology Transfection Axonal Transport chemistry.chemical_compound mental disorders medicine Serine Animals Humans Point Mutation Tyrosine Phosphorylation Cells Cultured Alpha-synuclein Neurons Lewy body Base Sequence Parkinson Disease Cell Biology Anatomy medicine.disease Recombinant Proteins nervous system diseases Cell biology Rats nervous system chemistry Axoplasmic transport Synuclein Mutagenesis Site-Directed alpha-Synuclein |
| Zdroj: | Journal of cell science. 117(Pt 7) |
| ISSN: | 0021-9533 |
| Popis: | Alpha-synuclein is a major protein constituent of Lewy bodies and mutations in alpha-synuclein cause familial autosomal dominant Parkinson's disease. One explanation for the formation of perikaryal and neuritic aggregates of alpha-synuclein, which is a presynaptic protein, is that the mutations disrupt alpha-synuclein transport and lead to its proximal accumulation. We found that mutant forms of alpha-synuclein, either associated with Parkinson's disease (A30P or A53T) or mimicking defined serine, but not tyrosine, phosphorylation states exhibit reduced axonal transport following transfection into cultured neurons. Furthermore, transfection of A30P, but not wild-type, alpha-synuclein results in accumulation of the protein proximal to the cell body. We propose that the reduced axonal transport exhibited by the Parkinson's disease-associated alpha-synuclein mutants examined in this study might contribute to perikaryal accumulation of alpha-synuclein and hence Lewy body formation and neuritic abnormalities in diseased brain. |
| Databáze: | OpenAIRE |
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