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Localized amyloids important in diseases outside the brain: lessons from the islets of Langerhans and the thoracic aorta
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
2011 (English)In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 278, no 20, 3918-3929 p.Article, review/survey (Refereed) Published
Abstract [en]

It has long been understood that amyloids can be lethal in systemic diseases. More recently, it has been accepted that local cerebral aggregation of the small peptide A beta is involved in the pathogenesis of Alzheimer's disease. Protein aggregation, with the generation of small amyloid deposits in specific organs, also occurs outside the central nervous system and often is associated with increased cell death. In this review, we discuss two lesser known but common localized amyloid fibril-forming proteins: the polypeptide hormone islet amyloid polypeptide (IAPP) and the lactadherin-derived peptide medin. IAPP aggregates and induces the depletion of islet beta-cells in type 2 diabetes and in islets transplanted into type 1 diabetic subjects. Initial amyloid deposition occurs intracellularly and parts of this amyloid consist of proIAPP. Medin derived from lactadherin expressed by smooth muscle cells aggregates into amyloid in certain arteries, particularly the thoracic aortic media layer, and may have a role in the generation of the potentially lethal conditions of thoracic aortic aneurysm and dissection.

Place, publisher, year, edition, pages
2011. Vol. 278, no 20, 3918-3929 p.
Keyword [en]
aortic aneurysm, aortic dissection, autophagy, giant cell arteritis, islet amyloid polypeptide, lactadherin, medin, type 2 diabetes
National Category
Cell and Molecular Biology Clinical Laboratory Medicine
Identifiers
URN: urn:nbn:se:uu:diva-160577DOI: 10.1111/j.1742-4658.2011.08298.xISI: 000295335500013PubMedID: 21834879OAI: oai:DiVA.org:uu-160577DiVA: diva2:451533
Available from: 2011-10-26 Created: 2011-10-26 Last updated: 2017-12-08Bibliographically approved

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Westermark, Gunilla T.Westermark, Per

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