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Titolo:
Apoptosis in amyotrophic lateral sclerosis: a review of the evidence
Autore:
Sathasivam, S; Ince, PG; Shaw, PJ;
Indirizzi:
Univ Sheffield, Sch Med, Dept Neurol, Sheffield S10 2RX, S Yorkshire, England Univ Sheffield Sheffield S Yorkshire England S10 2RX S Yorkshire, England Univ Sheffield, Dept Neuropathol, Sheffield S10 2RX, S Yorkshire, England Univ Sheffield Sheffield S Yorkshire England S10 2RX S Yorkshire, England
Titolo Testata:
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
fascicolo: 4, volume: 27, anno: 2001,
pagine: 257 - 274
SICI:
0305-1846(200108)27:4<257:AIALSA>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROGRAMMED CELL-DEATH; TRANSGENIC MOUSE MODEL; CENTRAL-NERVOUS-SYSTEM; MOTOR-NEURON DISEASE; TUMOR-SUPPRESSOR P53; DNA STRAND BREAKS; WILD-TYPE P53; CYTOCHROME-C; SUPEROXIDE-DISMUTASE; SPINAL-CORD;
Keywords:
apoptosis; amyotrophic lateral sclerosis; apoptosis-related molecules; Bcl-2 family members; caspases; death receptors; morphology of motor neurones; p53 pathway; TUNEL/ISEL staining;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
143
Recensione:
Indirizzi per estratti:
Indirizzo: Shaw, PJ Univ Sheffield, Sch Med, Dept Neurol, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England Univ Sheffield Beech Hill Rd Sheffield S Yorkshire England S10 2RX
Citazione:
S. Sathasivam et al., "Apoptosis in amyotrophic lateral sclerosis: a review of the evidence", NEUROP AP N, 27(4), 2001, pp. 257-274

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease primarily affecting the upper and lower motor neurones of the central nervous system. Recently, a lot of interest has been generated by the possibility that a mechanism of programmed cell death, termed apoptosis, is responsible for the motor neurone degeneration in this condition. Apoptosis is regulated through a variety of different pathways which interact and eventually lead to controlled cell death. Apart from genetic regulation, factors involved in the control of apoptosis include death receptors, caspases, Bcl-2 family of oncoproteins, inhibitor of apoptosis proteins (IAPs), inhibitors of IAPs, the p53 tumour suppressor protein and apoptosis-related molecules. The first part of this article will give an overview of the current knowledge of apoptosis. In the second part of this review, we will examine in detail the evidence for and against the contribution of apoptosis in motor neurone cell death in ALS, looking at cellular-, animal- and human post-mortem tissue-based models. In a chronic neurodegenerative disease such as ALS, conclusive evidence of apoptosis is likely to be difficult to detect, given the rapidity of the apoptotic cell death process in relation to the relatively slow time course of the disease. Although a complete picture of motor neurone death in ALS has not been fully elucidated, there is good and compelling evidence that a programmed cell death pathway operates in this disorder. The strongest body of evidence supporting this comes from the findings that, in ALS, changes in the levels of members of the Bcl-2 family of oncoproteins results in a predisposition towards-apoptosis, there is increasedexpression or activation of caspases-1 and -3, and the dying motor neurones in human cases exhibit morphological features reminiscent of apoptosis. Further supporting evidence comes from the detection of apoptosis-related molecules and anti-Fas receptor antibodies in human cases of ALS. However, the role of the p53 protein in cell death in ALS is at present unclear. An understanding of the mechanism of programmed cell death in ALS may provide important clues for areas of potential therapeutic intervention for neuroprotection in this devastating condition.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/09/20 alle ore 19:53:50