| Structural and morphological characterization of aggregated species of {alpha}-synuclein induced by docosahexaenoic acid. | |
| | |
MedLine Citation:
|
PMID: 21527634 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
The interaction of brain lipids with α-synuclein may play an important role in the pathogenesis of Parkinson disease (PD). Docosahexaenoic acid, DHA, is an abundant fatty acid of neuronal membranes and it is presents at high levels in brain areas with α-synuclein inclusions of patients with PD. In animal models, an increase of DHA content in the brain induces α-synuclein oligomer formation in vivo. However, it is not clear whether these oligomeric species are the precursors of the larger aggregates found in Lewy bodies of post-mortem PD brains. In order to characterize these species and to define the role of fatty acids in amyloid formation, we investigated the aggregation process of α-synuclein in the presence of DHA. We found that DHA readily promotes α-synuclein aggregation and that the morphology of these aggregates is dependent on the ratio between the protein and DHA. In the presence of a molar ratio protein/DHA of 1:10, amyloid-like fibrils are formed. These fibrils are morphologically different from those formed by α-synuclein alone and have a less packed structure. At a protein/DHA molar ratio of 1:50, we observe the formation of stable oligomers. Moreover, chemical modifications, methionine oxidations and protein-lipid adducts formation are induced by increasing concentration of DHA. The extent of these modifications defines the structure and the stability of aggregates. We also show that α-synuclein oligomers are more toxic if generated in the presence of DHA in dopaminergic neuronal cell lines, suggesting that these species might be important in the neurodegenerative process associated with PD. |
| | |
Authors:
|
Giorgia De Franceschi; Erica Frare; Micaela Pivato; Annalisa Relini; Amanda Penco; Elisa Greggio; Luigi Bubacco; Angelo Fontana; Patrizia Polverino de Laureto |
Related Documents
:
|
3020584 - Contrasting effects of fatty acids on oocyte maturation in several starfish species. 3132574 - Influence of substrate background on peripheral tissue responses to growth hormone. 9630454 - Endocrine factors modulate the phenobarbital-mediated induction of cytochromes p450 and... 18279024 - Metabolic effects of thyroid hormone derivatives. 9654404 - Dietary n-3 fatty acids alter angiotensin-induced contraction and 1,2-diacylglycerol fa... 17316224 - Waxing grave about adipocere: soft tissue change in an aquatic context. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-4-28 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
|
Created Date: 2011-4-29 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
University of Padova, Italy; |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: High mobility group box-1 (HMGB1; amphoterin) is required for zebrafish brain development.
Next Document: Radiation-triggered TNF{alpha}-NF{kappa}B cross signaling favors survival advantage in human neurobl...