The amyloid proteome: a systematic review and proposal of a protein classification system

Abstract

Amyloidosis is a disease caused by pathological fibril aggregation and deposition of proteins in different tissues and organs. Thirty-six fibril-forming proteins have been identified. So far, proteomic evaluation of amyloid focused on the detection and characterization of fibril proteins mainly for diagnostic purposes or to find novel fibril-forming proteins. However, amyloid deposits are a complex mixture of constituents that show organ-, tissue-, and amyloid-type specific patterns, that is the amyloid proteome. We carried out a comprehensive literature review on publications investigating amyloid via liquid chromatography coupled to tandem mass spectrometry, including but not limited to sample preparation by laser microdissection. Our review confirms the complexity and dynamics of the amyloid proteome, which can be divided into four functional categories: amyloid proteome-category 1 (APC1) includes exclusively fibrillary proteins found in the patient; APC2 includes potential fibril-forming proteins found in other types of amyloid; and APC3 and APC4 summarizes non-fibril proteins-some being amyloid signature proteins. Our categorization may help to systemically explore the nature and role of the amyloid proteome in the manifestation, progression, and clearance of disease. Further exploration of the amyloid proteome may form the basis for the development of novel diagnostic tools, thereby enabling the development of novel therapeutic targets.

Proteomic evidence for amyloidogenic cross-seeding in fibrinaloid microclots

“…A particular class of these more stable conformations involve a cross(ed)-β-sheet motif [52-58], and they become insoluble because they tend to aggregate and self-assemble; following their discovery by Virchow in 1854 (reviewed by Sipe and Cohen [59]) they are referred to as amyloids (see e.g. [60][61][62][63][64][65]). As is well known, they are intimately (if at best only partially) involved in a variety of diseases, including Alzheimer's [66] and Parkinson's.…”

Dissecting the Molecular Features of Systemic Light Chain (AL) Amyloidosis: Contributions from Proteomics

“…Although the physico-chemical relation between fibrils and amyloid-associated components is not yet defined, in vivo amyloid deposits are better described as an admixture of molecules, rather than simply as fibrils of a defined protein. A recently proposed classification system categorizes the amyloidproteome proteins into four functional categories: fibrillary proteins found in the patient; potential fibril-forming proteins found in other types of amyloid; non-fibril proteins, including some being amyloid signature proteins [91]. Assessment of whether amyloid composition relates to organ involving, to amyloidosis type and to disease severity would be of major interest for further understanding the molecular bases of these diseases [18,21].…”

Helical superstructures between amyloid and collagen VI in heart-derived fibrils from a patient with Light Chain Amyloidosis.

“…Ancillary proteins are reproducibly found in amyloid deposits, including heparan sulphate proteoglycan, serum amyloid P-component and various extracellular matrix elements (ECM) such as collagen 1,[26][27][28][29][30] . The ECM provides structural support for organs and tissues and is dynamically remodelled, controlling tissue homeostasis and modulating immune cell responses [31][32][33] .…”

“…The ECM provides structural support for organs and tissues and is dynamically remodelled, controlling tissue homeostasis and modulating immune cell responses [31][32][33] . As most prominent ECM component, collagens are frequently detected in deposits extracted from different amyloidosis types 27 . Co-purified collagens seem to affect directly amyloid formation and disease progression 27,[34][35][36][37][38][39] .…”

“…As most prominent ECM component, collagens are frequently detected in deposits extracted from different amyloidosis types 27 . Co-purified collagens seem to affect directly amyloid formation and disease progression 27,[34][35][36][37][38][39] .…”