Nerve growth factor attenuates oxidant-induced ß-amyloid neurotoxicity in sporadic Alzheimer's disease cybrids.
J Neurochem
; 114(6): 1605-18, 2010 Sep.
Article
em En
| MEDLINE
| ID: mdl-20561151
ABSTRACT
Although mitochondrial dysfunction has been linked to Alzheimer's disease (AD), it is not fully understood how this dysfunction may induce neuronal death. In this study, we show that transmitochondrial hybrid cells (cybrids) expressing mitochondrial genes from patients with sporadic AD (SAD) have substantial alterations in basal upstream tyrosine kinase signaling and downstream serine-threonine kinase signaling that are mediated by intracellular free radicals. This is associated with reduced tropomyocin receptor kinase (TrkA) and p75 neurotrophin receptor receptor expression that profoundly alters nerve growth factor signaling, increases generation of Aß and decreases viability. Many of these observed effects in SAD cybrids would be predicted to increase risk of premature neuronal death and reduce resistance to stressors and add further support for the pathogenic role of mtDNA expression in the pathogenesis of SAD.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Peptídeos beta-Amiloides
/
Receptores de Fator de Crescimento Neural
/
Doença de Alzheimer
/
Mitocôndrias
/
Fatores de Crescimento Neural
Tipo de estudo:
Prognostic_studies
Limite:
Aged
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article