Trehalose differentially inhibits aggregation and neurotoxicity of beta-amyloid 40 and 42
A key event in Alzheimer's disease (AD) pathogenesis is the conversion of the peptide beta-amyloid (Aβ) from its soluble monomeric form into various aggregated morphologies in the brain. Preventing aggregation of Aβ is being actively pursued as a primary therapeutic strategy for treating AD. Tr...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2005-10-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996105000628 |
| _version_ | 1819119821917257728 |
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| author | Ruitian Liu Hedieh Barkhordarian Sharareh Emadi Chan Beum Park Michael R. Sierks |
| author_facet | Ruitian Liu Hedieh Barkhordarian Sharareh Emadi Chan Beum Park Michael R. Sierks |
| author_sort | Ruitian Liu |
| collection | DOAJ |
| description | A key event in Alzheimer's disease (AD) pathogenesis is the conversion of the peptide beta-amyloid (Aβ) from its soluble monomeric form into various aggregated morphologies in the brain. Preventing aggregation of Aβ is being actively pursued as a primary therapeutic strategy for treating AD. Trehalose, a simple disaccharide, has been shown to be effective in preventing the deactivation of numerous proteins and in protecting cells against stress. Here, we show that trehalose is also effective in inhibiting aggregation of Aβ and reducing its cytotoxicity, although it shows differential effects toward Aβ40 and Aβ42. When co-incubated with Aβ40, trehalose inhibits formation of both fibrillar and oligomeric morphologies as determined by fluorescence staining and atomic force microscopy (AFM). However, when co-incubated with Aβ42, trehalose inhibits formation only of the fibrillar morphology, with significant oligomeric formation still present. When aggregated mixtures were incubated with SH-SY5Y cells, trehalose was shown to reduce the toxicity of Aβ40 mixtures, but not Aβ42. These results provide additional evidence that aggregation of Aβ into soluble oligomeric forms is a pathological step in AD and that Aβ42 in particular is more susceptible to forming these toxic oligomers than Aβ40. These results also suggest that the use of trehalose, a highly soluble, low-priced sugar, as part of a potential therapeutic cocktail to control Aβ peptide aggregation and toxicity warrants further study. |
| first_indexed | 2024-12-22T06:10:52Z |
| format | Article |
| id | doaj.art-0d5408e3da704e9aa72ea492ae4b3504 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-22T06:10:52Z |
| publishDate | 2005-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-0d5408e3da704e9aa72ea492ae4b35042022-12-21T18:36:15ZengElsevierNeurobiology of Disease1095-953X2005-10-012017481Trehalose differentially inhibits aggregation and neurotoxicity of beta-amyloid 40 and 42Ruitian Liu0Hedieh Barkhordarian1Sharareh Emadi2Chan Beum Park3Michael R. Sierks4Department of Chemical and Materials Engineering, Arizona State University, Box 876006, Tempe, AZ 85287-6006, USADepartment of Chemical and Materials Engineering, Arizona State University, Box 876006, Tempe, AZ 85287-6006, USADepartment of Chemical and Materials Engineering, Arizona State University, Box 876006, Tempe, AZ 85287-6006, USADepartment of Chemical and Materials Engineering, Arizona State University, Box 876006, Tempe, AZ 85287-6006, USACorresponding author. Fax: +1 480 965 0037.; Department of Chemical and Materials Engineering, Arizona State University, Box 876006, Tempe, AZ 85287-6006, USAA key event in Alzheimer's disease (AD) pathogenesis is the conversion of the peptide beta-amyloid (Aβ) from its soluble monomeric form into various aggregated morphologies in the brain. Preventing aggregation of Aβ is being actively pursued as a primary therapeutic strategy for treating AD. Trehalose, a simple disaccharide, has been shown to be effective in preventing the deactivation of numerous proteins and in protecting cells against stress. Here, we show that trehalose is also effective in inhibiting aggregation of Aβ and reducing its cytotoxicity, although it shows differential effects toward Aβ40 and Aβ42. When co-incubated with Aβ40, trehalose inhibits formation of both fibrillar and oligomeric morphologies as determined by fluorescence staining and atomic force microscopy (AFM). However, when co-incubated with Aβ42, trehalose inhibits formation only of the fibrillar morphology, with significant oligomeric formation still present. When aggregated mixtures were incubated with SH-SY5Y cells, trehalose was shown to reduce the toxicity of Aβ40 mixtures, but not Aβ42. These results provide additional evidence that aggregation of Aβ into soluble oligomeric forms is a pathological step in AD and that Aβ42 in particular is more susceptible to forming these toxic oligomers than Aβ40. These results also suggest that the use of trehalose, a highly soluble, low-priced sugar, as part of a potential therapeutic cocktail to control Aβ peptide aggregation and toxicity warrants further study.http://www.sciencedirect.com/science/article/pii/S0969996105000628Alzheimer's diseaseBeta-amyloidTrehaloseAggregationAtomic force microscopeCytotoxicity |
| spellingShingle | Ruitian Liu Hedieh Barkhordarian Sharareh Emadi Chan Beum Park Michael R. Sierks Trehalose differentially inhibits aggregation and neurotoxicity of beta-amyloid 40 and 42 Neurobiology of Disease Alzheimer's disease Beta-amyloid Trehalose Aggregation Atomic force microscope Cytotoxicity |
| title | Trehalose differentially inhibits aggregation and neurotoxicity of beta-amyloid 40 and 42 |
| title_full | Trehalose differentially inhibits aggregation and neurotoxicity of beta-amyloid 40 and 42 |
| title_fullStr | Trehalose differentially inhibits aggregation and neurotoxicity of beta-amyloid 40 and 42 |
| title_full_unstemmed | Trehalose differentially inhibits aggregation and neurotoxicity of beta-amyloid 40 and 42 |
| title_short | Trehalose differentially inhibits aggregation and neurotoxicity of beta-amyloid 40 and 42 |
| title_sort | trehalose differentially inhibits aggregation and neurotoxicity of beta amyloid 40 and 42 |
| topic | Alzheimer's disease Beta-amyloid Trehalose Aggregation Atomic force microscope Cytotoxicity |
| url | http://www.sciencedirect.com/science/article/pii/S0969996105000628 |
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