Proteoglycans and amyloid fibrillogenesis.
A brief discussion of the general structure of proteoglycans is followed by a description of the diverse nature of amyloids. Using the murine form of inflammation-associated (AA) amyloid, we have examined the temporal and anatomical relationship between the heparan sulfate proteoglycan, its mRNA and AA amyloid deposition in vivo. The in vitro effect of heparan sulfate on the secondary structure of amyloid precursors, and on amyloid peptides, suggests that this interaction is important in amyloidogenesis. The relationship of these two components likely reflects a more general process taking place between basement membrane proteins (which may be synthesized by a variety of cell types within and outside the CNS) and amyloid precursors. A general definition of in vivo amyloid deposits emerges from these considerations as do concepts for interfering with amyloidogenesis. Preliminary results showing the effect of small molecule aliphatic sulfonates and sulfates on in vitro amyloid beta-protein fibrillogenesis and AA amyloidogenesis in vivo supports the general process presented and suggests therapeutic strategies for treating amyloid-based diseases.
Kisilevsky
R
R
Department of Pathology, Queen's University, Kingston General Hospital, Ontario, Canada.
Fraser
P
P
D000595:Amino Acid Sequence; D000682:Amyloid / Q000096:biosynthesis* / Q000737:chemistry; D000686:Amyloidosis / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D011509:Proteoglycans / Q000737:chemistry / Q000378:metabolism*
D000682:Amyloid; D006497:Heparan Sulfate; D008565:Membrane Proteins; D011509:Proteoglycans