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Titolo:
Dityrosine cross-linking promotes formation of stable alpha-synuclein polymers - Implication of nitrative and oxidative stress in the pathogenesis ofneurodegenerative synucleinopathies
Autore:
Souza, JM; Giasson, BI; Chen, QP; Lee, VMY; Ischiropoulos, H;
Indirizzi:
Childrens Hosp Philadelphia, Stokes Res Inst, Abramson Ctr 416D, Philadelphia, PA 19104 USA Childrens Hosp Philadelphia Philadelphia PA USA 19104 lphia, PA 19104 USA Univ Penn, Med Ctr, Dept Biochem & Biophys, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 & Biophys, Philadelphia, PA 19104 USA Univ Penn, Med Ctr, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USAUniv Penn Philadelphia PA USA 19104 t Dis Res, Philadelphia, PA 19104 USA Univ Penn, Med Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA UnivPenn Philadelphia PA USA 19104 & Lab Med, Philadelphia, PA 19104 USA Univ Republ, Fac Med, Dept Bioquim, Montevideo 11800, Uruguay Univ RepublMontevideo Uruguay 11800 Bioquim, Montevideo 11800, Uruguay
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 24, volume: 275, anno: 2000,
pagine: 18344 - 18349
SICI:
0021-9258(20000616)275:24<18344:DCPFOS>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
MULTIPLE SYSTEM ATROPHY; LEWY BODY DISEASE; GLIAL CYTOPLASMIC INCLUSIONS; PARKINSONS-DISEASE; NACP/ALPHA-SYNUCLEIN; ALZHEIMERS-DISEASE; IN-VITRO; TYROSINE NITRATION; NITRIC-OXIDE; BODIES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Ischiropoulos, H Childrens Hosp Philadelphia, Stokes Res Inst, Abramson Ctr 416D, 34th St &Civ Ctr Blvd, Philadelphia, PA 19104 USA Childrens Hosp Philadelphia 34th St & Civ Ctr Blvd Philadelphia PA USA 19104
Citazione:
J.M. Souza et al., "Dityrosine cross-linking promotes formation of stable alpha-synuclein polymers - Implication of nitrative and oxidative stress in the pathogenesis ofneurodegenerative synucleinopathies", J BIOL CHEM, 275(24), 2000, pp. 18344-18349

Abstract

Intracellular proteinaceous aggregates are hallmarks of many common neurodegenerative disorders, and recent studies have shown that alpha-synuclein is a major component of several pathological intracellular inclusions, including Lewy bodies in Parkinson's disease (PD) and glial cell inclusions in multiple system atrophy. However, the molecular mechanisms underlying alpha-synuclein aggregation into filamentous inclusions remain unknown. Since oxidative and nitrative stresses are potential pathogenic mediators of PD and other neurodegenerative diseases, we asked if oxidative and/or nitrative events alter alpha-synuclein and induce it to aggregate. Here we show that exposure of human recombinant a-synuclein to nitrating agents (peroxynitrite/CO2 or myeloperoxidase/H2O2/nitrite) induces formation of nitrated alpha-synuclein oligomers that are highly stabilized due to covalent cross-linking via the oxidation of tyrosine to form o,o'-dityrosine. We also demonstrate that oxidation and nitration of pre-assembled alpha-synuclein filaments stabilize these filaments to withstand denaturing conditions and enhance formation of SDS-insoluble, heat-stable high molecular mass aggregates. Thus, these data suggest that oxidative and nitrative stresses are involved in mechanisms underlying the pathogenesis of Lewy bodies and glial cell inclusionsin PD and multiple system atrophy, respectively, as well as alpha-synuclein pathologies in other synucleinopathies.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 06:13:41