Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
Abstract
Parkinson's disease (PD) is a common neurodegenerative disorder with a lifetime incidence of approximately 2 percent. A pattern of familial aggregation has been documented for the disorder, and it was recently reported that a PD susceptibility gene in a large Italian kindred is located on the long arm of human chromosome 4. A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype. This finding of a specific molecular alteration associated with PD will facilitate the detailed understanding of the pathophysiology of the disorder.
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In vitro, progranulin promotes the autoactivation of procathepsin D into the mature form, enhancing its activity.
“In vitro, progranulin promotes the autoactivation of the proprotein of cathepsin D into the mature form, thus enhancing its activity.132”
From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [132]
All known autosomal dominant point mutations that cause PD reside within the 11-residue repeat motifs of αSyn.
“all known autosomal dominant point mutations that cause PD reside within these repeat motifs, specifically A30P[120], E46K[121], A53T[122], G51D[123], and H50Q[124]”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [122]
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- Authors
- Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., Stenroos, E. S., Chandrasekharappa, S., Athanassiadou, A., Papapetropoulos, T., Johnson, W. G., Lazzarini, A. M., Duvoisin, R. C., Di Iorio, G., Golbe, L. I., & Nussbaum, R. L.
- Affiliations
- National Institutes of Health (US)
- M. H. Polymeropoulos, C. Lavedan, E. Leroy, S. E. Ide, A. Dehejia, J. Rubenstein, R. Boyer, R. L. Nussbaum, Laboratory of Genetic Disease Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892–1430, USA.
- Corresponding author
- Polymeropoulos, Mihael H.
- Lavedan, Christian
- Leroy, Elisabeth
- ORCID
- Venue
- Science
- Published
- 1997-06-27
- Volume
- 276
- Issue
- 5321
- Pages
- 2045-2047
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2150656456
- Cited by
- 8,240
- References
- 22
- Citations by year
- 2026: 199 · 2025: 275 · 2024: 309 · 2023: 305 · 2022: 339 · 2021: 346 · 2020: 374 · 2019: 332 · 2018: 328 · 2017: 366 · 2016: 277 · 2015: 281 · 2014: 309 · 2013: 323 · 2012: 300
- FWCI
- 133.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- Parkinson's disease, SNCA mutations, familial aggregation, autosomal dominant inheritance, chromosome 4, presynaptic proteins, neurodegeneration, genetic susceptibility
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Chromosome Mapping, Chromosomes, Human, Pair 4, Female, Genes, Dominant, Genetic Markers, Greece, Humans, Italy, Male, Molecular Sequence Data, Nerve Tissue Proteins, Parkinson Disease, Pedigree, Phenotype, Polymerase Chain Reaction, Point Mutation, Protein Structure, Secondary, Age of Onset, Synucleins, alpha-Synuclein
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