The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Molecular Crowding Accelerates Fibrillization of α-Synuclein: Could an Increase in the Cytoplasmic Protein Concentration Induce Parkinson's Disease?
Abstract
Parkinson's disease (PD) is one of many neurodegenerative diseases that are characterized by amyloid fibril formation. Alpha-synuclein is a primary component of the fibrillar neuronal inclusions, known as Lewy bodies, that are diagnostic of PD. In addition, the alpha-synuclein gene is linked to familial PD. Fibril formation by alpha-synuclein proceeds via discrete beta-sheet-rich oligomers, or protofibrils, that are consumed as fibrils grow. Both FPD mutations accelerate formation of protofibrils, suggesting that these intermediates, rather than the fibril product, trigger neuronal loss. In idiopathic PD, other factors may be responsible for accelerating protofibril formation by wild-type alpha-synuclein. One possible factor could be molecular crowding in the neuronal cytoplasm. We demonstrate here that crowding using inert polymers significantly reduced the lag time for protofibril formation and the conversion of the protofibril to the fibril, but did not affect the morphology of either species. Physiologically realistic changes in the degree of in vitro crowding have significant kinetic consequences. Thus, nonspecific changes in the total cytoplasmic protein concentration, induced by cell volume changes and/or altered protein degradation, could promote formation of and stabilize the alpha-synuclein protofibril.
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Cites
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Implications of macromolecular crowding for protein assembly
Minton, A. P. (2000) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(99)00045-7 · Cited by 649
Influence of excluded volume upon macromolecular structure and associations in ‘crowded” media
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Effects of dextran on the self-association of human spectrin
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Cited by
Fabrication of novel biomaterials through molecular self-assembly
Zhang, S. (2003) · Nature Biotechnology · doi:10.1038/nbt874 · Cited by 3,347
Conformational constraints for amyloid fibrillation: the importance of being unfolded
Uversky, V. N., & Fink, A. L. (2004) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2003.12.008 · Cited by 1,015
α‐Synuclein aggregation nucleates through liquid‐liquid phase separation
Ray, S., Singh, N., Kumar, R., Patel, K., Pandey, S., Datta, D., Mahato, J., Panigrahi, R., Navalkar, A., Mehra, S., et al. (2020) · Nature Chemistry · doi:10.1038/s41557-020-0465-9 · Cited by 863
Liu, Y., Fallon, L., Lashuel, H. A., Liu, Z., & Lansbury, P. T. (2002) · Cell · doi:10.1016/s0092-8674(02)01012-7 · Cited by 785
Self-citationα-Synuclein misfolding and Parkinson's disease
Breydo, L., Wu, J. W., & Uversky, V. N. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.10.002 · Cited by 657
Metadata
- Authors
- Shtilerman, M. D., Ding, T. T., & Lansbury, P. T.
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2002-02-27
- Volume
- 41
- Issue
- 12
- Pages
- 3855-3860
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- OpenAlex
- W2085987859
- Cited by
- 281
- References
- 5
- FWCI
- 10.25
- Type
- journal article
- Language
- en
- Open access
- closed
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