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Titolo:
Microglial secreted cathepsin B induces neuronal apoptosis
Autore:
Kingham, PJ; Pocock, JM;
Indirizzi:
Univ Coll London, Inst Neurol, Dept Neurochem, Cell Signalling Lab, LondonWC1N 1PJ, England Univ Coll London London England WC1N 1PJ ng Lab, LondonWC1N 1PJ, England
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 5, volume: 76, anno: 2001,
pagine: 1475 - 1484
SICI:
0022-3042(200103)76:5<1475:MSCBIN>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROGRAMMED CELL-DEATH; AMYLOID BETA-PROTEIN; CHROMOGRANIN-A; CYSTATIN-C; CONSTITUTIVE SECRETION; CYSTEINE PROTEINASES; LYSOSOMAL PROTEASES; ALZHEIMERS-DISEASE; RAT-BRAIN; MACROPHAGES;
Keywords:
Alzheimer's disease; apoptosis; cathepsin B; chromogranin A; microglia; neurotoxicity;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Pocock, JM Univ Coll London, Inst Neurol, Dept Neurochem, Cell Signalling Lab, 1 Wakefield St, London WC1N 1PJ, England Univ Coll London 1 Wakefield St London England WC1N 1PJ ngland
Citazione:
P.J. Kingham e J.M. Pocock, "Microglial secreted cathepsin B induces neuronal apoptosis", J NEUROCHEM, 76(5), 2001, pp. 1475-1484

Abstract

Activated microglia release a number of substances that can influence neuronal signalling and survival. Here we report that microglia stimulated withthe peptide chromogranin A (CGA), secreted the cysteine protease, cathepsin B. Conditioned medium from CGA exposed microglia was neurotoxic to the HT22 hippocampal cell line and to primary cultures of cerebellar granule neurones. In both neuronal cell types, the neurotoxicity could be significantlyattenuated with z-FA-fmk or by depletion of microglial conditioned medium with cathepsin B antibody. Conditioned medium from activated microglia or cathepsin B alone induced neuronal apoptosis and caspase 3 activation. Our data indicate that CGA-activated microglia can trigger neuronal apoptosis and that this may be mediated through the secretion of cathepsin B. Since cathepsins may also play a role in the amyloidogenic processing of amyloid precursor protein, these results may have significance for tissue damage and neuronal loss in the neuropathology of Alzheimer's disease.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/04/20 alle ore 23:21:00