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Axonal motor protein KIF5A and associated cargo deficits in multiple sclerosis lesional and normal-appearing white matter

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)227–241
Number of pages15
JournalNeuropathology and Applied Neurobiology
Volume43
Issue number3
Early online date1 Apr 2016
DOIs
DateAccepted/In press - 5 Jan 2016
DateE-pub ahead of print - 1 Apr 2016
DatePublished (current) - Apr 2017

Abstract

Aims

Understanding the causes of axonal pathology remains a key goal in the pursuit of new therapies to target disease progression in MS. Anterograde axonal transport of many proteins vital for axonal viability is mediated by the motor protein KIF5A, which has been linked to several neurological diseases. This study aimed to investigate the expression of KIF5A protein and its associated cargoes: amyloid precursor protein (APP) and neurofilament (NF) in post-mortem MS and control white matter and to determine if KIF5A expression is influenced by the presence of MS risk single nucleotide polymorphisms (SNPs) identified in the region of the KIF5A gene.

Methods

Using immunoblotting assays we analyzed the expression of KIF5A, APP and NF phospho-isoforms in 23 MS cases and 12 controls.

Results

We found a significant reduction in KIF5A and associated cargoes in MS white matter and an inverse correlation between KIF5A and APP/NF protein levels. Furthermore, homozygous carriers of MS risk gene SNPs show significantly lower levels of KIF5A protein compared to MS patients with no copies of the risk SNPs.

Conclusions

We conclude that reduced expression of axonal motor KIF5A may have important implications in determining axonal transport deficits and ongoing neurodegeneration in MS.

    Research areas

  • amyloid precursor protein, axonal transport, KIF5A, multiple sclerosis, neurofilament, single nucleotide polymorphism, white matter

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    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Wiley at http://onlinelibrary.wiley.com/doi/10.1111/nan.12305/abstract. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 487 KB, PDF document

    Licence: CC BY-NC

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