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Sulfated glycosaminoglycans in protein aggregation diseases

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Abstract

Protein aggregation diseases are characterized by intracellular or extracellular deposition of misfolded and aggregated proteins. These aggregated deposits contain multiple proteinaceous and non-protein components that are thought to play critical roles in the etiology and pathogenesis of protein aggregation diseases in vivo. One of these components, the sulfated glycosaminoglycans (GAGs), includes heparan sulfate, chondroitin sulfate, and keratan sulfate. The sulfated GAGs are negatively charged heteropolysaccharides expressed in all mammalian tissues. Enzymatically generated structural patterns and the degree of sulfation in GAGs determine GAGs’ specific interactions with their protein ligands. Here, we review the potential roles of the sulfated GAGs in the pathogenesis and progression of protein aggregation diseases from a perspective of their sulfation modification. We also discuss the possibility of sulfated GAGs as therapeutic targets for protein aggregation diseases.

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Abbreviations

Aβ:

Amyloid β-protein

CAA:

Cerebral amyloid angiopathy

HS:

Heparan sulfate

GAG:

Glycosaminoglycan

AD:

Alzheimer’s disease

PD:

Parkinson’s disease

CS:

Chondroitin sulfate

CSPG:

Chondroitin sulfate proteoglycan

KS:

Keratan sulfate

AA:

Amyloid A

AL:

Amyloid immunoglobulin light chain

ATTR:

Amyloid transthyretin

2-m:

Amyloid β2-microglobulin

apoA-I:

Apolipoprotein A-I

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Acknowledgements

This work was supported by grants from the Japanese Health and Labour Sciences Research (Comprehensive Research on Aging and Health H22-007 to K.U.), by Grants-in-Aid from the Ministry of Education, Science, Sports, and Culture (24590349 and 15 K08265 to K.U. and B-15 K19488 to K.N.), and in part by the Takeda Science Foundation (K.U.) and the Kobayashi International Scholarship Foundation (K.U.). We would like to apologize to those whose works could not be directly cited due to space constraints.

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Correspondence to Kenji Uchimura.

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Nishitsuji, K., Uchimura, K. Sulfated glycosaminoglycans in protein aggregation diseases. Glycoconj J 34, 453–466 (2017). https://doi.org/10.1007/s10719-017-9769-4

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