Sci. Aging Knowl. Environ., 14 January 2004
Vol. 2004, Issue 2, p. pe3
[DOI: 10.1126/sageke.2004.2.pe3]


Glycation Stimulates Amyloid Formation

Mark E. Obrenovich, and Vincent M. Monnier

The authors are in the Department of Pathology at Case Western Reserve University, Cleveland, OH 44106, USA. E-mail: vmm3{at} (V.M.M.)

Key Words: amyloid • glycation • protein aggregation • protein folding • {beta} sheet • cross-{beta} structure

Abstract: Amyloidosis comprises a group of systemic and localized diseases with varied clinical presentations. In these diseases, amyloid forms when proteins with a largely {alpha}-helical structure lose their original conformation and are converted into a predominantly {beta}-sheet form, thereby increasing their propensity to form highly insoluble and fibrillar aggregates. Most soluble amyloid precursor proteins have substantial {beta}-pleated sheet secondary structure, and extensive {beta}-pleated sheet structure occurs in all of the deposited fibrils. The aberrant deposition of proteins as cellular inclusions or plaques in the form of amyloid fibrils is a characteristic hallmark of all amyloid diseases (or amyloidoses) and of the so-called conformational diseases. Environmental and genetic factors are known to be involved, but the mechanism by which this process happens still is poorly understood. Here we report a new finding from the Dutch group of Gebbink and colleagues, which points to the posttranslational process of glycation as a key mechanism in the formation of amyloid. These researchers showed that glycation causes albumin, a globular protein with a largely {alpha}-helical structure, to adopt a {beta}-pleated sheet structure and the quaternary structural element known as the cross-{beta} conformation. These are features commonly shared by all amyloids. This research is the first to show glycation as a predisposing factor for amyloidosis.

Citation: M. E. Obrenovich, V. M. Monnier, Glycation Stimulates Amyloid Formation. Sci. Aging Knowl. Environ. 2004 (2), pe3 (2004).

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