Reduced axonal motor protein expression in non-lesional grey matter in multiple sclerosis

被引:18
|
作者
Hares, K. [1 ]
Kemp, K. [1 ]
Rice, C. [1 ]
Gray, E. [1 ]
Scolding, N. [1 ]
Wilkins, A. [1 ]
机构
[1] Univ Bristol, Multiple Sclerosis & Stem Cell Grp, Sch Clin Sci, Bristol BS16 1JB, Avon, England
基金
英国生物技术与生命科学研究理事会; 英国医学研究理事会;
关键词
Axonal injury; axonal transport; grey matter; KIF5A; KIF2IB; KIFIB; kinesin; multiple sclerosis; protein expression; HEAVY-CHAIN KIF5A; TRANSPORT; SUSCEPTIBILITY; NEURODEGENERATION; NEUROFILAMENTS; ASSOCIATION; DISEASES; NEURONS; KIF21B; LOCUS;
D O I
10.1177/1352458513508836
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background: Multiple sclerosis (MS) is a neurological disease characterised by central nervous system inflammation, dennyelination, axonal degeneration and neuronal injury. Preventing neuronal and axon damage is of paramount importance in attempts to prevent disease progression. Intact axonal transport mechanisms are crucial to axonal integrity and evidence suggests these mechanisms are disrupted in MS. Anterograde axonal transport is mediated to a large extent through the kinesin superfamily proteins. Recently, certain kinesin superfamily proteins (KIF5A, KIF I B and KIF2IB) were implicated in MS pathology. Objectives: To investigate the expression of KIF5A, KIF2IB and KIFIB in MS and control post-mortem grey matter. Methods: Using both quantitative real-time polymerase chain reaction (PCR) and lmmunodot-blots assays, we analysed the expression of kinesin superfamily proteins in 27 MS cases and 13 control cases not linked to neurological disease. Results: We have shown significant reductions in KIF5A, KIF2IB and KIFIB messenger ribonucleic acid (mRNA) expression and also KIF5A protein expression in MS grey matter, as compared to control grey matter. Conclusion: We have shown significant reductions in mRNA and protein levels of axonal motor proteins in the grey matter of MS cases, which may have important implications for the pathogenesis of neuronal/axonal injury in the disease.
引用
收藏
页码:812 / 821
页数:10
相关论文
共 50 条
  • [1] Axonal motor protein KIF5A and associated cargo deficits in multiple sclerosis lesional and normal-appearing white matter
    Hares, K.
    Redondo, J.
    Kemp, K.
    Rice, C.
    Scolding, N.
    Wilkins, A.
    NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 2017, 43 (03) : 227 - 241
  • [2] Dendritic cells are abundant in non-lesional gray matter in multiple sclerosis
    Cudrici, Cornelia
    Ito, Takahiro
    Zafranskaia, Ekaterina
    Niculescu, Florin
    Mullen, Kathenne M.
    Vlaicu, Sonia
    Judge, Susan I. V.
    Calabresi, Peter A.
    Rus, Horea
    EXPERIMENTAL AND MOLECULAR PATHOLOGY, 2007, 83 (02) : 198 - 206
  • [3] Non-lesional white matter changes in pediatric multiple sclerosis and monophasic demyelinating disorders
    Tillema, J. M.
    Leach, J.
    Pirko, I.
    MULTIPLE SCLEROSIS JOURNAL, 2012, 18 (12) : 1754 - 1759
  • [4] The cognitive relevance of non-lesional damage to cortical networks in people with multiple sclerosis
    Krijnen, Eva A.
    Broeders, Tommy A. A.
    Noteboom, Samantha
    van Dam, Maureen
    Bajrami, Albulena
    Bouman, Piet M.
    Barkhof, Frederik
    Uitdehaag, Bernard M. J.
    Klawiter, Eric C.
    Koubiyr, Ismail
    Schoonheim, Menno M.
    JOURNAL OF NEUROLOGY, 2024, 271 (06) : 3203 - 3214
  • [5] Non-lesional white matter in relapsing-remitting multiple sclerosis assessed by multicomponent T2 relaxation
    Bontempi, Pietro
    Rozzanigo, Umberto
    Marangoni, Sabrina
    Fogazzi, Elena
    Ravanelli, Daniele
    Cazzoletti, Lucia
    Giometto, Bruno
    Farace, Paolo
    BRAIN AND BEHAVIOR, 2023, 13 (12):
  • [6] Non-lesional white matter changes depicted by q-space diffusional MRI correlate with clinical disabilities in multiple sclerosis
    Motegi, Haruhiko
    Kufukihara, Kenji
    Kitagawa, Satoshi
    Sekiguchi, Koji
    Hata, Junichi
    Fujiwara, Hirokazu
    Jinzaki, Masahiro
    Okano, Hideyuki
    Nakamura, Masaya
    Iguchi, Yasuyuki
    Nakahara, Jin
    JOURNAL OF THE NEUROLOGICAL SCIENCES, 2024, 456
  • [7] Grey matter pathology in multiple sclerosis
    Bö, L
    Geurts, JJG
    Mörk, SJ
    van der Valk, P
    ACTA NEUROLOGICA SCANDINAVICA, 2006, 113 : 48 - 50
  • [8] Grey matter pathology in multiple sclerosis
    Vercellino, M
    Plano, F
    Votta, B
    Mutani, R
    Giordana, MT
    Cavalla, P
    JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2005, 64 (12): : 1101 - 1107
  • [9] Progression of regional grey matter atrophy in multiple sclerosis
    Eshaghi, Arman
    Marinescu, Razvan V.
    Young, Alexandra L.
    Firth, Nicholas C.
    Prados, Ferran
    Cardoso, M. Jorge
    Tur, Carmen
    De Angelis, Floriana
    Cawley, Niamh
    Brownlee, Wallace J.
    De Stefano, Nicola
    Stromillo, M. Laura
    Battaglini, Marco
    Ruggieri, Serena
    Gasperini, Claudio
    Filippi, Massimo
    Rocca, Maria A.
    Rovira, Alex
    Sastre-Garriga, Jaume
    Geurts, Jeroen J. G.
    Vrenken, Hugo
    Wottschel, Viktor
    Leurs, Cyra E.
    Uitdehaag, Bernard
    Pirpamer, Lukas
    Enzinger, Christian
    Ourselin, Sebastien
    Wheeler-Kingshott, Claudia A. Gandini
    Chard, Declan
    Thompson, Alan J.
    Barkhof, Frederik
    Alexander, Daniel C.
    Ciccarelli, Olga
    BRAIN, 2018, 141 : 1665 - 1677
  • [10] Oxidative injury in multiple sclerosis cerebellar grey matter
    Kemp, Kevin
    Redondo, Juliana
    Hares, Kelly
    Rice, Claire
    Scolding, Neil
    Wilkins, Alastair
    BRAIN RESEARCH, 2016, 1642 : 452 - 460