Extracellular deposition of beta-amyloid upon p53-dependent neuronal cell death in transgenic mice.
AUTOR(ES)
LaFerla, F M
RESUMO
The finding that intracellular expression of the beta-amyloid protein (Abeta) under a neuron-specific promoter led progressively to degeneration and death of neurons in the brains of transgenic mice provides a unique opportunity to utilize this animal model to both understand the mechanism that underlies neuronal cell death and define the complexity of events which may ensue. We observed a correlation between Abeta accumulation in selective neurons and activation of p53, a protein that has been implicated in the induction of apoptosis. Histological and immunohistochemical evaluations of adjacent brain sections suggest that expression of p53 is accompanied by nuclear DNA fragmentation. In certain regions with marked neuronal cell death, extracellular deposition of A(beta) became evident, together with the local activation of astrocytes. Interestingly, the neuritic structures underlying the Abeta deposits showed altered synaptophysin immunoreactivity and morphologic evidence for damage. This transgenic mouse model suggests that intracellular generation of the Abeta protein not only leads to the death of the neuron but may also functionally impair neighboring neurons as well. It further offers a mechanism whereby neuritic plaques may be derived.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=507596Documentos Relacionados
- Expression of the human beta-amyloid precursor protein gene from a yeast artificial chromosome in transgenic mice.
- Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans.
- Inhibition of Alzheimer's disease beta-amyloid aggregation, neurotoxicity and in vivo deposition
- Generation of beta-amyloid in the secretory pathway in neuronal and nonneuronal cells.
- Reversible in vitro growth of Alzheimer disease beta-amyloid plaques by deposition of labeled amyloid peptide.