Microglia and Chitotriosidase in Multiple Sclerosis

Microglia and Chitotriosidase in Multiple Sclerosis

Bonetti Bruno, Musumeci Salvatore, Sotgiu Stefano
Published: European Neurology - Volume 3 Issue 2
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Initial biochemical investigations led to the unexpected discovery that plasma samples of patients with Gaucher disease (GD), a lysosomal storage disease, had a several hundred-fold elevated ability to hydrolyse chitin, a polymer of beta 1,4-linked N-acetylglucosamine that is largely diffuse in nature.1 Later, the same investigators observed that lipid-laden activated macrophages accumulating in GD tissues were able to secrete exceedingly high levels of an enzyme able to cleave chitin and artificial chitotrioside substrates, therefore named chitotriosidase (Chit).2,3 The measurement of plasma Chit activity has now also found an application in the clinical monitoring of patients with Fabry disease.4

Chit is a member of the mammalian chitinase family. It is mainly synthesised by activated macrophages and also by immature neutrophils5 as a 50kDa protein, proteolitically cleaved and predominantly secreted. Its natural substrate, chitin, is known for being an integral part of an arthropod’s exoskeleton.6–9 Its content is variable within species and is reported to account for up to 20% of the fungal cell wall.10,11 So far, no definitive mammalian chitin synthetase has been documented, although a pathogenic role of this oligosaccharide in vertebrates has been reported. Chitin is utilised in the enhancement of the inflammatory roles of macrophages and neutrophils11,12 and, in such instances, may also modulate the cerebral microglial activation documented in neuroinflammatory and neurodegenerative diseases.13,14

An important question arises when considering that chitin is absent in humans. However, the fact that the Chit gene is present and conserved in rodents and primates15 argues in favour of a biological role of this enzyme.

Chit, Chitin and the Central Nervous System
In pathological conditions Chit has achieved an increasingly important role as a marker of some neurological diseases,16 perhaps by virtue of the peculiar immune condition that characterises the brain. Nonetheless, physiological conditions such as ageing have also been found to correlate with a progressive increase of plasmatic Chit activity.17,18 This might suggest that the innate immune system is involved in protecting the healthy human organism from cell damage that occurs during ageing, perhaps linked to oxidative processes.19

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