Only amyloidogenic inermediates of transthyretin induce apoptosis
2002 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, Vol. 294, no 2, 309-314 p.Article in journal (Refereed) Published
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. (c) 2002 Elsevier Science (USA).
Place, publisher, year, edition, pages
2002. Vol. 294, no 2, 309-314 p.
Amyloid, Transthyretin, Cytotoxicity, Apoptosis, Free radicals
IdentifiersURN: urn:nbn:se:umu:diva-4476DOI: 10.1016/S0006-291X(02)00465-5PubMedID: 12051711OAI: oai:DiVA.org:umu-4476DiVA: diva2:143597