The effect of time-dependent macromolecular crowding on the kinetics of protein aggregation: a simple model for the onset of age-related neurodegenerative disease
A linear increase in the concentration of inert macromolecules with time is incorporated into simple excluded volume models for protein condensation or fibrillation. Such models predict a long latent period during which no significant amount of protein aggregates, followed by a steep increase in th...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-08-01
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| Series: | Frontiers in Physics |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphy.2014.00048/full |
| _version_ | 1811270872480088064 |
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| author | Allen P. Minton |
| author_facet | Allen P. Minton |
| author_sort | Allen P. Minton |
| collection | DOAJ |
| description | A linear increase in the concentration of inert macromolecules with time is incorporated into simple excluded volume models for protein condensation or fibrillation. Such models predict a long latent period during which no significant amount of protein aggregates, followed by a steep increase in the total amount of aggregate. The elapsed time at which these models predict half-conversion of model protein to aggregate varies by less than a factor of two when the intrinsic rate constant for condensation or fibril growth of the protein is varied over many orders of magnitude. It is suggested that this concept can explain why the symptoms of neurodegenerative diseases associated with the aggregation of very different proteins and peptides appear at approximately the same advanced age in humans. |
| first_indexed | 2024-04-12T22:10:50Z |
| format | Article |
| id | doaj.art-7f5bdecc2752400b844d847c5e05a403 |
| institution | Directory Open Access Journal |
| issn | 2296-424X |
| language | English |
| last_indexed | 2024-04-12T22:10:50Z |
| publishDate | 2014-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physics |
| spelling | doaj.art-7f5bdecc2752400b844d847c5e05a4032022-12-22T03:14:46ZengFrontiers Media S.A.Frontiers in Physics2296-424X2014-08-01210.3389/fphy.2014.00048104550The effect of time-dependent macromolecular crowding on the kinetics of protein aggregation: a simple model for the onset of age-related neurodegenerative diseaseAllen P. Minton0National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of HealthA linear increase in the concentration of inert macromolecules with time is incorporated into simple excluded volume models for protein condensation or fibrillation. Such models predict a long latent period during which no significant amount of protein aggregates, followed by a steep increase in the total amount of aggregate. The elapsed time at which these models predict half-conversion of model protein to aggregate varies by less than a factor of two when the intrinsic rate constant for condensation or fibril growth of the protein is varied over many orders of magnitude. It is suggested that this concept can explain why the symptoms of neurodegenerative diseases associated with the aggregation of very different proteins and peptides appear at approximately the same advanced age in humans.http://journal.frontiersin.org/Journal/10.3389/fphy.2014.00048/fullparkinsonismAlzheimer's dementiaexcluded volumeprotein condensationprotein fibrillation |
| spellingShingle | Allen P. Minton The effect of time-dependent macromolecular crowding on the kinetics of protein aggregation: a simple model for the onset of age-related neurodegenerative disease Frontiers in Physics parkinsonism Alzheimer's dementia excluded volume protein condensation protein fibrillation |
| title | The effect of time-dependent macromolecular crowding on the kinetics of protein aggregation: a simple model for the onset of age-related neurodegenerative disease |
| title_full | The effect of time-dependent macromolecular crowding on the kinetics of protein aggregation: a simple model for the onset of age-related neurodegenerative disease |
| title_fullStr | The effect of time-dependent macromolecular crowding on the kinetics of protein aggregation: a simple model for the onset of age-related neurodegenerative disease |
| title_full_unstemmed | The effect of time-dependent macromolecular crowding on the kinetics of protein aggregation: a simple model for the onset of age-related neurodegenerative disease |
| title_short | The effect of time-dependent macromolecular crowding on the kinetics of protein aggregation: a simple model for the onset of age-related neurodegenerative disease |
| title_sort | effect of time dependent macromolecular crowding on the kinetics of protein aggregation a simple model for the onset of age related neurodegenerative disease |
| topic | parkinsonism Alzheimer's dementia excluded volume protein condensation protein fibrillation |
| url | http://journal.frontiersin.org/Journal/10.3389/fphy.2014.00048/full |
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