Document Detail


Lipid peroxidation product, 4-hydroxy-2-nonenal, promotes seeding-capable oligomer formation and cell-to-cell transfer of α-synuclein.
MedLine Citation:
PMID:  22867050     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Aims: Abnormal accumulation of α-synuclein aggregates is one of the key pathological features of many neurodegenerative movement disorders and dementias. These pathological aggregates propagate into larger brain regions as the disease progresses, with the associated clinical symptoms becoming increasingly severe and complex. However, the factors that induce α-synuclein aggregation and spreading of the aggregates remain elusive. Herein, we have evaluated the effects of the major lipid peroxidation byproduct, 4 hydroxy-2-nonenal (HNE), on α-synuclein oligomerization and cell-to-cell transmission of this protein. Results: Incubation with HNE promoted the oligomerization of recombinant human α-synuclein via adduct formation at the lysine and histidine residues. HNE-induced α-synuclein oligomers evidence a little β-sheet structure and are distinct from amyloid fibrils at both conformation and ultrastructure levels. Nevertheless, the HNE-induced oligomers are capable of seeding the amyloidogenesis of monomeric α-synuclein under in vitro conditions. When neuronal cells were treated with HNE, both the translocation of α-synuclein into vesicles and the release of this protein from cells were increased. Neuronal cells can internalize HNE-modified α-synuclein oligomers, and HNE treatment increased the cell-to-cell transfer of α-synuclein proteins. Conclusion: These results indicate that HNE induces the oligomerization of α-synuclein through covalent modification and promotes the cell-to-cell transfer of seeding-capable oligomers, thereby contributing to both the initiation and spread of α-synuclein aggregates.
Authors:
Eun-Jin Bae; Dong-Hwan Ho; Eunbi Park; Jin Woo Jung; Kyungcho Cho; Ji Hye Hong; He-Jin Lee; Kwang Pyo Kim; Seung-Jae Lee
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-7
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  -     ISSN:  1557-7716     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Konkuk University, Biomedical Science and Technology, Seoul, Korea, Republic of; agarci@hanmail.net.
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