Apoptosis is directly related to intracellular amyloid accumulation in a cell line derived from the cerebral cortex of a trisomy 16 mouse, an animal model of Down syndrome
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- 作者：Christian Arriagada ; Miguel Bustamante ; Illani Atwater ; Eduardo Rojas ; Raú ; l Caviedes ; Pablo Caviedes
- 关键词：β ; -Amyloid ; Murine Ts16 ; Down syndrome model ; Recycling ; Apoptosis ; Intracellular accumulation
- 刊名：Neuroscience Letters
- 出版年：2010
- 出版时间：5 February 2010
- 年：2010
- 卷：470
- 期：1
- 页码：81-85
- 全文大小：514 K
文摘
Human Down syndrome (DS) represents the most frequent cause of mental retardation associated to a genetic condition. DS also exhibits a characteristic early onset of neuropathology indistinguishable from that observed in Alzheimer's disease (AD), namely the deposition of the β-amyloid peptide. Early endosomal dysfunction has been described in individuals with DS and AD, suggesting an important role of this subcellular compartment in the onset and progression of the pathology. On the other hand, cholesterol activates the amyloidogenic processing pathway for the amyloid precursor protein, and the lipoprotein receptor-related peptide interacts with the β-amyloid peptide. In the present work, using cell lines derived from the cortex of both normal and trisomy 16 mice (Ts16), an animal model of DS, we showed that the application of exogenous β-amyloid has cytotoxic effects, expressed in decreased viability and increased apoptosis. Supplementation of the culture media with cholesterol associated to lipoprotein increased cell viability in both cell lines, but apoptosis decreased only in the normal cell line. Further, intracellular β-amyloid content was elevated in trisomic cells following cholesterol treatment, with higher values in the trisomic cell line. Immunocytochemical detection showed intracellular accumulation of exogenous β-amyloid in Rab4-positive compartments, which are known to be associated to endosomal recycling. The results suggest that the intracellular β-amyloid pool plays a central role in apoptosis-mediated cell death in the trisomic condition.