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Titolo:
INCREASED PRODUCTION OF AMYLOID PRECURSOR PROTEIN PROVIDES A SUBSTRATE FOR CASPASE-3 IN DYING MOTONEURONS
Autore:
BARNES NY; LI L; YOSHIKAWA K; SCHWARTZ LM; OPPENHEIM RW; MILLIGAN CE;
Indirizzi:
WAKE FOREST UNIV,SCH MED,DEPT NEUROBIOL & ANAT,MED CTR BLVD WINSTON SALEM NC 27157 WAKE FOREST UNIV,SCH MED,DEPT NEUROBIOL & ANAT WINSTON SALEM NC 27157 WAKE FOREST UNIV,SCH MED,NEUROSCI PROGRAM WINSTON SALEM NC 27157 OSAKA UNIV,INST PROT RES,DIV REGULAT MACROMOL FUNCT SUITA OSAKA 565 JAPAN UNIV MASSACHUSETTS,DEPT BIOL AMHERST MA 01003
Titolo Testata:
The Journal of neuroscience
fascicolo: 15, volume: 18, anno: 1998,
pagine: 5869 - 5880
SICI:
0270-6474(1998)18:15<5869:IPOAPP>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROGRAMMED CELL-DEATH; EMBRYO SPINAL-CORD; NERVE GROWTH-FACTOR; ALZHEIMERS-DISEASE; GENE-EXPRESSION; CHICK-EMBRYO; BETA-PROTEIN; SYMPATHETIC NEURONS; C-JUN; POSTMITOTIC NEURONS;
Keywords:
APOPTOSIS; ALZHEIMERS DISEASE; AMYLOID PRECURSOR PROTEIN; BETA-AMYLOID; CPP-32; ICE-LIKE PROTEASES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
68
Recensione:
Indirizzi per estratti:
Citazione:
N.Y. Barnes et al., "INCREASED PRODUCTION OF AMYLOID PRECURSOR PROTEIN PROVIDES A SUBSTRATE FOR CASPASE-3 IN DYING MOTONEURONS", The Journal of neuroscience, 18(15), 1998, pp. 5869-5880

Abstract

Biochemical and molecular mechanisms of neuronal cell death are currently an area of intense research. It is well documented that the lumbar spinal motoneurons of the chick embryo undergo a period of naturallyoccurring programmed cell death (PCD) requiring new gene expression and activation of caspases. To identify genes that exhibit changed expression levels in dying motoneurons, we used a PCR-based subtractive hybridization protocol to identify messages uniquely expressed in motoneurons deprived of trophic support as compared with their healthy counterparts. We report that one upregulated message in developing motoneurons undergoing cell death is the mRNA for amyloid precursor protein (APP). Increased levels of APP and beta-amyloid protein are also detected within dying motoneurons. The predicted peptide sequence of APP indicates two potential cleavage sites for caspase-3 (CPP-32), a caspase activated in dying motoneurons. When peptide inhibitors of caspase-3 are administered to motoneurons destined to undergo PCD, decreased levels of APP protein and greatly reduced p-amyloid production are observed. Furthermore, we show that APP is cleaved by caspase-3. Our results suggest that differential gene expression results in increased levels of APP, providing a potential substrate for one of the cell death-activated caspases that may ultimately cause the demise of the cell. These results, combined with information on the toxic role of APP and its proteolytic by-product beta-amyloid, in the neurodegenerative disease Alzheimer's, suggest that events of developmental PCD may be reactivatedin early stages of pathological neurodegeneration.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 10:19:32