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Heparan sulphates, amyloidosis and neurodegeneration

C. Vera, J.A. Álvarez-Orozco, A. Maïza, S. Chantepie, R.N. Chehín, M.O. Ouidja, D. Papy-Garcia [REV NEUROL 2017;65:457-468] PMID: 29130469 DOI: https://doi.org/10.33588/rn.6510.2017235

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Volumen 65 | Number 10 | Nº of views of the article 11.756 | Nº of PDF downloads 290 | Article publication date 16/11/2017

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ABSTRACT

INTRODUCTION A number of neurodegenerative disorders have been linked directly to the accumulation of amyloid fibres. These fibres are made up of proteins or peptides with altered structures and which join together in vivo in association with heparan sulphate-type polysaccharides. AIMS. To examine the most recent concepts in the biology of heparan sulphates and their role in the aggregation of the peptide Abeta, of tau protein, of alpha-synuclein and of prions. The study also seeks to analyse their implications in neurodegenerative disorders such as Alzheimers and Parkinsons disease and prion diseases. DEVELOPMENT. In vitro, heparan sulphates have played an important role in the process of oligomerisation and fibrillation of amyloidogenic proteins or peptides, in the stabilisation of these bodies and their resistance to proteolysis, thereby participating in the formation of a wide range of amyloid fibres. Heparan sulphates have also been related to the internalisation of pro-amyloid fibres during the process of intercellular propagation (spreading), which is considered to be crucial in the development of proteinopathies, the best example of which is Alzheimers disease. CONCLUSION. This study suggests that the fine structures of heparan sulphates, their localisation in cells and tissues, together with their local concentration, may regulate the amyloidosis processes. The advances made in the understanding of this area of glyconeurobiology will make it possible to improve the understanding of the cell and molecular mechanisms underlying the neurodegenerative process. KeywordsAbeta Alpha-synuclein Alzheimers disease Glycosaminoglycans Heparan sulphates Neurodegeneration Parkinsons disease Prion Protein aggregation Tau protein CategoriesDemencia Infecciones Neurodegeneración Trastornos del movimiento

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Heparan sulphates, amyloidosis and neurodegeneration