Only amyloidogenic intermediates of transthyretin induce apoptosis |
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Authors: | Andersson Karin Olofsson Anders Nielsen Ellen Holm Svehag Sven-Erik Lundgren Erik |
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Affiliation: | Department of Cell and Molecular Biology, Ume? University, S-901 87 Ume?, Sweden. |
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Abstract: | In diseases like Alzheimer's disease and familial amyloidotic polyneuropathy (FAP) amyloid deposits co-localize with areas of neurodegeneration. FAP is associated with mutations of the plasma protein transthyretin (TTR). We can here show an apoptotic effect of amyloidogenic mutants of TTR on a human neuroblastoma cell line. Toxicity could be blocked by catalase indicating a free oxygen radical dependent mechanism. The toxic effect was dependent on the state of aggregation and unexpectedly mature fibrils from FAP-patients who failed to exert an apoptotic response. Morphological studies revealed a correlation between toxicity and the presence of immature amyloid. Thus, we can show that toxicity is associated with early stages of fibril formation and propose that mature full-length fibrils represent an inert end stage, which might serve as a rescue mechanism. |
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Keywords: | Amyloid Transthyretin Cytotoxicity Apoptosis Free radicals |
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