The role of innate immunity in mucopolysaccharide diseases. Issue 5 (13th December 2018)

• Record Type: Journal Article
• Authors: Parker, Helen; Bigger, Brian W.
• Other Names: Kielian Tammy guestEditor.
• Is Part Of: Journal of neurochemistry. Volume 148:Issue 5(2019)
• Page Start: 639
• Page End: 651
• Publication Date: 2018-12-13
• Subjects: heparan sulphate -- inflammasome -- inflammation -- innate immunity -- lysosomal dysfunction -- mucopolysaccharidosis; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.14632
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract: Mucopolysaccharidoses are lysosomal storage disorders characterised by accumulation of abnormal pathological glycosaminoglycans, cellular dysfunction and widespread inflammation, resulting in progressive cognitive and motor decline. Lysosomes are important mediators of immune cell function, and therefore accumulation of glycosaminoglycans (GAGs) and other abnormal substrates could affect immune function and directly impact on disease pathogenesis. This review summarises current knowledge with regard to inflammation in mucopolysaccharidosis, with an emphasis on the brain and outlines a potential role for GAGs in induction of inflammation. We propose a model by which the accumulation of GAGs and other factors may impact on innate immune signalling with particular focus on the Toll‐like receptor 4 pathway. Innate immunity appears to have a dominating role in mucopolysaccharidosis; however, furthering understanding of innate immune signalling would have significant impact on highlighting novel anti‐inflammatory therapeutics for use in mucopolysaccharide diseases. This article is part of the Special Issue "Lysosomal Storage Disorders" . Abstract : Mucopolysaccharidoses are lysosomal storage disorders characterised by accumulation of abnormal glycosaminoglycans, cellular dysfunction and widespread inflammation. Lysosomes are critical mediators of immunity, and therefore lysosomal substrate accumulation could affect immune function and directly impact on disease pathogenesis. In this review, we summarise the current knowledge with regard to inflammation in mucopolysaccharidosis with an emphasis on the brain. We propose a model by which the accumulation of GAGs may impact on innate immune signalling with particular focus on the TLR4 pathway. Furthering our understanding of inflammatory signalling in lysosomal storage disease would have significant impact on highlighting novel anti‐inflammatory therapeutics. This article is part of the Special Issue "Lysosomal Storage Disorders" .