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Titolo:
Direct binding and functional coupling of alpha-synuclein to the dopamine transporters accelerate dopamine-induced apoptosis
Autore:
Lee, FJS; Liu, F; Pristupa, ZB; Niznik, HB;
Indirizzi:
Ctr Addict & Mental Hlth, Mol Neurobiol Lab, Toronto, ON M5T 1R8, Canada Ctr Addict & Mental Hlth Toronto ON Canada M5T 1R8 to, ON M5T 1R8, Canada Univ Toronto, Dept Pharmacol, Toronto, ON M5S 1A8, Canada Univ Toronto Toronto ON Canada M5S 1A8 macol, Toronto, ON M5S 1A8, Canada Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada Univ Toronto Toronto ON Canada M5S 1A8 d Sci, Toronto, ON M5S 1A8, Canada
Titolo Testata:
FASEB JOURNAL
fascicolo: 6, volume: 15, anno: 2001,
pagine: 916 - 926
SICI:
0892-6638(200104)15:6<916:DBAFCO>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-KINASE-C; A-BETA COMPONENT; CENTRAL-NERVOUS-SYSTEM; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; SUBSTANTIA-NIGRA; LEWY BODIES; CELL-DEATH; NEURODEGENERATIVE DISORDERS;
Keywords:
DA uptake; cell death; coimmunoprecipitation; GST fusion proteins; Parkinson's disease;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
84
Recensione:
Indirizzi per estratti:
Indirizzo: Lee, FJS Ctr Addict & Mental Hlth, Mol Neurobiol Lab, 250 Coll St, Toronto, ON M5T 1R8, Canada Ctr Addict & Mental Hlth 250 Coll St Toronto ON CanadaM5T 1R8 da
Citazione:
F.J.S. Lee et al., "Direct binding and functional coupling of alpha-synuclein to the dopamine transporters accelerate dopamine-induced apoptosis", FASEB J, 15(6), 2001, pp. 916-926

Abstract

Mutations in alpha -synuclein, a protein highly enriched in presynaptic terminals, have been implicated in the expression of familial forms of Parkinson's disease (PD) whereas native alpha -synuclein is a major component of intraneuronal inclusion bodies characteristic of PD and other neurodegenerative disorders. Although overexpression of human a-synuclein induces dopaminergic nerve terminal degeneration, the molecular mechanism by which alpha -synuclein contributes to the degeneration of these pathways remains enigmatic, We report here that alpha -synuclein complexes with the presynaptic human dopamine transporter (hDAT) in both neurons and cotransfected cells through the direct binding of the non-A beta amyloid component of alpha -synuclein to the carboxyl-terminal tail of the hDAT, alpha -Synuclein-hDAT complex formation facilitates the membrane clustering of the DAT, thereby accelerating cellular dopamine uptake and dopamine-induced cellular apoptosis, Since the selective vulnerability of dopaminergic neurons in PD has been ascribed in part to oxidative stress as a result of the cellular overaccumulation of dopamine or dopamine-like molecules by the presynaptic DAT, these data provide mechanistic insight into the mode by which the activity of these two proteins may give rise to this process.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 18:41:05