Heparan sulfate proteoglycans in amyloidosis.
Amyloidosis is a generic term for a group of diseases characterized by deposits in different organ systems of insoluble materials composed mainly of distinct fibrillar proteins named amyloid. Besides amyloid, heparan sulfate proteoglycan (HSPG), is commonly found in most amyloid deposits, suggesting that HS/HSPG may be functionally involved in the pathogenesis of amyloidosis. HS or HSPG is found to interact with a number of amyloid proteins, displaying a promoting effect on amyloid fibrilization in vitro. In addition, HS is reported to be involved in processing amyloid precursor proteins and mediate amyloid toxicity. Although little is known about the in vivo mechanisms regarding the codeposition of HS with amyloid proteins in different amyloid diseases, experiments carried out in animal models, especially in transgenic mouse model where HS molecular structure is modified, support an active role for HS in amyloidogenesis. Further experimental evidence is required to strengthen these in vivo findings at a molecular level. Animal models that express mutant forms of HS due to knockout of the enzymes involved in glycosaminoglycan (GAG) biosynthesis are expected to provide valuable tools for studying the implications of HS, as well as other GAGs, in amyloid disorders.
Zhang
Xiao
X
Department of Public Health and Caring Sciences, Molecular Geriatrics, University of Uppsala, Uppsala, Sweden.
Li
Jin-Ping
JP
D000686:Amyloidosis / Q000378:metabolism*; D000818:Animals; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout
D019812:Heparan Sulfate Proteoglycans