title: EGCG Inhibited Lipofuscin Formation Based on Intercepting Amyloidogenic β-Sheet-Rich Structure Conversion.
abstract: BACKGROUND
  Lipofuscin (LF) is formed during lipid peroxidation and sugar glycosylation by carbonyl-amino crosslinks with biomacrolecules, and accumulates slowly within postmitotic cells. The environmental pollution, modern dietary culture and lifestyle changes have been found to be the major sources of reactive carbonyl compounds in vivo. Irreversible carbonyl-amino crosslinks induced by carbonyl stress are essentially toxiferous for aging-related functional losses in modern society. Results show that (-)-epigallocatechin gallate (EGCG), the main polyphenol in green tea, can neutralize the carbonyl-amino cross-linking reaction and inhibit LF formation, but the underlying mechanism is unknown.
  
  
  RESULTS
  We explored the mechanism of the neutralization process from protein, cell, and animal levels using spectrofluorometry, infrared spectroscopy, conformation antibodies, and electron microscopy. LF demonstrated an amyloidogenic β-sheet-rich with antiparallel structure, which accelerated the carbonyl-amino crosslinks formation and disrupted proteolysis in both PC12 cells and D-galactose (D-gal)-induced brain aging mice models. Additionally, EGCG effectively inhibited the formation of the amyloidogenic β-sheet-rich structure of LF, and prevented its conversion into toxic and on-pathway aggregation intermediates, thereby cutting off the carbonyl-amino crosslinks.
  
  
  CONCLUSIONS
  Our study indicated that the amyloidogenic β-sheet structure of LF may be the core driving force for carbonyl-amino crosslinks further formation, which mediates the formation of amyloid fibrils from native state of biomacrolecules. That EGCG exhibits anti-amyloidogenic β-sheet-rich structure properties to prevent the LF formation represents a novel strategy to impede the development of degenerative processes caused by ageing or stress-induced premature senescence in modern environments.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, 100191, China.
authors.forename: Shuxian
authors.initials: S
authors.lastname: Cai
authors.affiliation: Co-Innovation Center for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha, 410128, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, 100191, China.
authors.forename: Kewu
authors.initials: K
authors.lastname: Zeng
authors.affiliation: Co-Innovation Center for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha, 410128, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Co-Innovation Center for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha, 410128, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Zhong
authors.affiliation: Co-Innovation Center for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha, 410128, China.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, 100191, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, 100191, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Tu
authors.affiliation: Co-Innovation Center for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha, 410128, China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D008062:Lipofuscin / Q000096:biosynthesis*; D051379:Mice; D016716:PC12 Cells; D051381:Rats
chemical_list: D008062:Lipofuscin; D002392:Catechin; C045651:epigallocatechin gallate