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Titolo:
A one-hit model of cell death in inherited neuronal degenerations (vol 406, pg 195, 2000)
Autore:
Clarke, G; Collins, RA; Leavitt, BR; Andrews, DF; Hayden, MR; Lumsden, CJ; McInnes, RR;
Indirizzi:
Hosp Sick Children, Res Inst, Program Dev Biol, Toronto, ON M5G 1X8, Canada Hosp Sick Children Toronto ON Canada M5G 1X8 Toronto, ON M5G 1X8, Canada Hosp Sick Children, Res Inst, Genet Program, Toronto, ON M5G 1X8, Canada Hosp Sick Children Toronto ON Canada M5G 1X8 Toronto, ON M5G 1X8, Canada Univ Toronto, Inst Med Sci, Dept Mol & Med Genet, Toronto, ON M5S 1A8, Canada Univ Toronto Toronto ON Canada M5S 1A8 Genet, Toronto, ON M5S 1A8, Canada Univ Toronto, Inst Med Sci, Dept Pediat, Toronto, ON M5S 1A8, Canada Univ Toronto Toronto ON Canada M5S 1A8 ediat, Toronto, ON M5S 1A8, Canada Univ Toronto, Inst Med Sci, Dept Med, Toronto, ON M5S 1A8, Canada Univ Toronto Toronto ON Canada M5S 1A8 t Med, Toronto, ON M5S 1A8, Canada Univ British Columbia, Dept Med Genet, Ctr Mol Med & Therapeut, Vancouver,BC V5Z 4H4, Canada Univ British Columbia Vancouver BC Canada V5Z 4H4 uver,BC V5Z 4H4, Canada Univ Toronto, Dept Stat, Toronto, ON M5S 3G3, Canada Univ Toronto TorontoON Canada M5S 3G3 Stat, Toronto, ON M5S 3G3, Canada
Titolo Testata:
NATURE
fascicolo: 6819, volume: 409, anno: 2001,
pagine: 542 -
SICI:
0028-0836(20010125)409:6819<542:AOMOCD>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
IDIOPATHIC PARKINSONISM; RETINITIS-PIGMENTOSA; RETINAL DEGENERATION; ALZHEIMERS-DISEASE; MUTANT MOUSE; LIGHT; NEURODEGENERATION; PATHOGENESIS; PROGRESSION; GLUTAMATE;
Tipo documento:
Correction, Addition
Natura:
Periodico
Settore Disciplinare:
Agriculture,Biology & Environmental Sciences
Life Sciences
Physical, Chemical & Earth Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Clarke, G Hosp Sick Children, Res Inst, Program Dev Biol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada Hosp Sick Children 555 Univ Ave Toronto ON CanadaM5G 1X8 Canada
Citazione:
G. Clarke et al., "A one-hit model of cell death in inherited neuronal degenerations (vol 406, pg 195, 2000)", NATURE, 409(6819), 2001, pp. 542

Abstract

In genetic disorders associated with premature neuronal death, symptoms may not appear for years or decades. This delay in clinical onset is often assumed to reflect the occurrence of age-dependent cumulative damage(1-6). For example, it has been suggested that oxidative stress disrupts metabolism in neurological degenerative disorders by the cumulative damage of essential macromolecules(1,4,7). A prediction of the cumulative damage hypothesis is that the probability of cell death will increase over time. Here we show in contrast that the kinetics of neuronal death in 12 models of photoreceptor degeneration, hippocampal neurons undergoing excitotoxic cell death(8), a mouse model of cerebellar degeneration(9) and Parkinson's(10) and Huntington's diseases are all exponential and better explained by mathematical models in which the risk of cell death remains constant or decreases exponentially with age. These kinetics argue against the cumulative damage hypothesis; instead, the time of death of any neuron is random. Our findings are most simply accommodated by a 'one-hit' biochemical model in which mutation imposes a mutant steady state on the neuron and a single event randomly initiates cell death. This model appears to be common to many forms of neurodegeneration and has implications for therapeutic strategies.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 01:34:17