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Titolo:
Caspase-6 role in apoptosis of human neurons, amyloidogenesis, and Alzheimer's disease
Autore:
LeBlanc, A; Liu, H; Goodyer, C; Bergeron, C; Hammond, J;
Indirizzi:
Mortimer B Davis Jewish Gen Hosp, Bloomfield Ctr Res Aging, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada Mortimer B Davis Jewish Gen Hosp Montreal PQ Canada H3T 1E2 T 1E2, Canada McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ H3T 1E2, Canada McGill Univ Montreal PQ Canada H3T 1E2 surg, Montreal, PQ H3T 1E2, Canada McGill Univ, Dept Pediat, Montreal, PQ H3H 1P3, Canada McGill Univ Montreal PQ Canada H3H 1P3 diat, Montreal, PQ H3H 1P3, Canada Univ Toronto, Dept Pathol, Toronto, ON M5S 1A8, Canada Univ Toronto Toronto ON Canada M5S 1A8 athol, Toronto, ON M5S 1A8, Canada
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 33, volume: 274, anno: 1999,
pagine: 23426 - 23436
SICI:
0021-9258(19990813)274:33<23426:CRIAOH>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMYLOID PRECURSOR PROTEIN; PROGRAMMED CELL-DEATH; RAT HIPPOCAMPAL-NEURONS; ENZYME-LIKE PROTEASES; GENE-EXPRESSION; BETA-PROTEIN; IN-VIVO; C-JUN; POSTMITOTIC NEURONS; CYSTEINE PROTEASES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
65
Recensione:
Indirizzi per estratti:
Indirizzo: LeBlanc, A Mortimer B Davis Jewish Gen Hosp, Bloomfield Ctr Res Aging, Lady Davis Inst Med Res, 3755 Ch Cote Ste Catherine, Montreal, PQ H3T 1E2, Canada Mortimer B Davis Jewish Gen Hosp 3755 Ch Cote Ste Catherine Montreal PQCanada H3T 1E2
Citazione:
A. LeBlanc et al., "Caspase-6 role in apoptosis of human neurons, amyloidogenesis, and Alzheimer's disease", J BIOL CHEM, 274(33), 1999, pp. 23426-23436

Abstract

Neuronal cell death, neurofibrillary tangles, and amyloid beta peptide (A beta) deposition depict Alzheimer's disease (AD) pathology, but neuronal loss correlates best with dementia. We have shown that increased production of A beta is a consequence of neuronal apoptosis, suggesting that apoptosis activates proteases involved in amyloid precursor protein (APP) processing,Here, we investigate key effecters of cell death, caspases, in human neuronal apoptosis and APP processing. We find that caspase-6 is activated and responsible for neuronal apoptosis by serum deprivation. Caspase-6 activity precedes the time of commitment to neuronal apoptosis by 10 h, indicating possible activity without subsequent apoptosis, Inhibition of caspase-6 activity prevents serum deprivation-mediated increase of A beta. Caspase-6 directly cleaves APP at the C terminus and generates a C-terminal fragment of 3kDa (Capp3) and an A beta-containing 6.5-kDa fragment, Capp6.5, that increases in serum-deprived neurons. A pulse-chase experiment reveals a precursor-product relationship between Capp6.5, intracellular A beta, and secreted A beta, indicating a potential alternate amyloidogenic pathway. Caspase-6 proenzyme is present in adult human brain tissue, and the p10 active caspase-6 fragment is detected in AD brain tissue. These results indicate a possible alternate pathway for APP amyloidogenic processing in human neurons and a potential implication for this pathway in the neuronal demise of AD.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 19:43:18