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

Kelly M Hares; Juliana Redondo; Kevin C Kemp; Claire M Rice; Neil J Scolding; Alastair Wilkins

doi:10.1111/nan.12305

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

Kelly M Hares, Juliana Redondo, Kevin C Kemp, Claire M Rice, Neil J Scolding, Alastair Wilkins

Research output: Contribution to journal › Article (Academic Journal) › peer-review

20 Citations (Scopus)

544 Downloads (Pure)

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.

Original language	English
Pages (from-to)	227–241
Number of pages	15
Journal	Neuropathology and Applied Neurobiology
Volume	43
Issue number	3
Early online date	1 Apr 2016
DOIs	https://doi.org/10.1111/nan.12305
Publication status	Published - Apr 2017

Keywords

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

Access to Document

10.1111/nan.12305

Full-text PDF (accepted author manuscript)
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, 488 KBLicence: CC BY-NC

Handle.net

Persistent link

Dr Claire M Rice
- C.M.Ricebristol.acuk
- Bristol Medical School (THS) - Associate Professor in Neuroinflammation
- Multiple Sclerosis and Stem Cell Group
- Bristol Neuroscience
Person: Academic , Member, Group lead

Cite this

@article{86b102bf6fb448349f8027f7c8c6d8c7,

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

abstract = "AimsUnderstanding 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.MethodsUsing immunoblotting assays we analyzed the expression of KIF5A, APP and NF phospho-isoforms in 23 MS cases and 12 controls.ResultsWe 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.ConclusionsWe conclude that reduced expression of axonal motor KIF5A may have important implications in determining axonal transport deficits and ongoing neurodegeneration in MS.",

keywords = "amyloid precursor protein, axonal transport, KIF5A, multiple sclerosis, neurofilament, single nucleotide polymorphism, white matter",

author = "Hares, {Kelly M} and Juliana Redondo and Kemp, {Kevin C} and Rice, {Claire M} and Scolding, {Neil J} and Alastair Wilkins",

year = "2017",

month = apr,

doi = "10.1111/nan.12305",

language = "English",

volume = "43",

pages = "227–241",

journal = "Neuropathology and Applied Neurobiology",

issn = "0305-1846",

publisher = "Wiley-Blackwell",

number = "3",

}

TY - JOUR

T1 - Axonal motor protein KIF5A and associated cargo deficits in multiple sclerosis lesional and normal-appearing white matter

AU - Hares, Kelly M

AU - Redondo, Juliana

AU - Kemp, Kevin C

AU - Rice, Claire M

AU - Scolding, Neil J

AU - Wilkins, Alastair

PY - 2017/4

Y1 - 2017/4

N2 - AimsUnderstanding 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.MethodsUsing immunoblotting assays we analyzed the expression of KIF5A, APP and NF phospho-isoforms in 23 MS cases and 12 controls.ResultsWe 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.ConclusionsWe conclude that reduced expression of axonal motor KIF5A may have important implications in determining axonal transport deficits and ongoing neurodegeneration in MS.

AB - AimsUnderstanding 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.MethodsUsing immunoblotting assays we analyzed the expression of KIF5A, APP and NF phospho-isoforms in 23 MS cases and 12 controls.ResultsWe 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.ConclusionsWe conclude that reduced expression of axonal motor KIF5A may have important implications in determining axonal transport deficits and ongoing neurodegeneration in MS.

KW - amyloid precursor protein

KW - axonal transport

KW - KIF5A

KW - multiple sclerosis

KW - neurofilament

KW - single nucleotide polymorphism

KW - white matter

U2 - 10.1111/nan.12305

DO - 10.1111/nan.12305

M3 - Article (Academic Journal)

C2 - 26785938

VL - 43

SP - 227

EP - 241

JO - Neuropathology and Applied Neurobiology

JF - Neuropathology and Applied Neurobiology

SN - 0305-1846

IS - 3

ER -

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

Abstract

Keywords

Access to Document

Handle.net

Fingerprint

Profiles

Dr Claire M Rice

Cite this