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The Effect of Glycosaminoglycans (GAGs) on Amyloid Aggregation and Toxicity
- Source :
- Molecules, Vol 20, Iss 2, Pp 2510-2528 (2015), Molecules
- Publication Year :
- 2015
- Publisher :
- MDPI AG, 2015.
-
Abstract
- Amyloidosis is a protein folding disorder in which normally soluble proteins are deposited extracellularly as insoluble fibrils, impairing tissue structure and function. Charged polyelectrolytes such as glycosaminoglycans (GAGs) are frequently found associated with the proteinaceous deposits in tissues of patients affected by amyloid diseases. Experimental evidence indicate that they can play an active role in favoring amyloid fibril formation and stabilization. Binding of GAGs to amyloid fibrils occurs mainly through electrostatic interactions involving the negative polyelectrolyte charges and positively charged side chains residues of aggregating protein. Similarly to catalyst for reactions, GAGs favor aggregation, nucleation and amyloid fibril formation functioning as a structural templates for the self-assembly of highly cytotoxic oligomeric precursors, rich in β-sheets, into harmless amyloid fibrils. Moreover, the GAGs amyloid promoting activity can be facilitated through specific interactions via consensus binding sites between amyloid polypeptide and GAGs molecules. We review the effect of GAGs on amyloid deposition as well as proteins not strictly related to diseases. In addition, we consider the potential of the GAGs therapy in amyloidosis.
- Subjects :
- Amyloid
amyloid aggregation
Pharmaceutical Science
Review
Protein aggregation
Fibril
Protein Aggregation, Pathological
amyloid toxicity inhibition
Analytical Chemistry
Glycosaminoglycan
lcsh:QD241-441
Amyloid disease
lcsh:Organic chemistry
Drug Discovery
mental disorders
medicine
Animals
Humans
Physical and Theoretical Chemistry
Binding site
Chemistry
Amyloidosis
Organic Chemistry
P3 peptide
medicine.disease
Biochemistry
glycosaminoglycans
Chemistry (miscellaneous)
Molecular Medicine
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 20
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....34b34522c716017a7c2b7238bbe11c03