Remyelination and ageing: Reversing the ravages of time

被引:82
作者
Neumann, Bjoern [1 ]
Segel, Michael [1 ]
Chalut, Kevin J. [1 ]
Franklin, Robin J. M. [1 ]
机构
[1] Univ Cambridge, Jeffrey Cheah Biomed Ctr, Wellcome Trust Med Res Council Cambridge Stem Cel, Cambridge CB2 0AWH, England
基金
英国生物技术与生命科学研究理事会; 欧洲研究理事会; 英国惠康基金;
关键词
Remyelination; stem cell; ageing; oligodendrocyte progenitor cell; MULTIPLE-SCLEROSIS; PROGENITOR CELLS; ADULT CNS; DEMYELINATION; AGE; DIFFERENTIATION; MYELIN; OLIGODENDROCYTES; SUPPORT; REJUVENATION;
D O I
10.1177/1352458519884006
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Remyelination is a neuroprotective regenerative response to demyelination that restores saltatory conduction and decreases the vulnerability of axons to irreversible degeneration. It is a highly efficient process: however, as with all regenerative processes, its efficiency declines with ageing. Here we argue that this age-related decline in remyelination has a major impact on the natural history of multiple sclerosis (MS), a disease often of several decades' duration. We describe recent work on (1) how ageing changes the function of oligodendrocyte progenitor cells (OPCs), the cells primarily responsible for generating new myelin-forming oligodendrocytes in remyelination, (2) how these changes are induced by age-related changes in the OPC niche and (3) how these changes can be reversed, thereby opening up the possibility of therapeutically maintaining remyelination efficiency throughout the disease, preserving axonal health and treating the progressive phase of MS.
引用
收藏
页码:1835 / 1841
页数:7
相关论文
共 67 条
[1]   Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions [J].
Absinta, Martina ;
Sati, Pascal ;
Schindler, Matthew ;
Leibovitch, Emily C. ;
Ohayon, Joan ;
Wu, Tianxia ;
Meani, Alessandro ;
Filippi, Massimo ;
Jacobson, Steven ;
Cortese, Irene C. M. ;
Reich, Daniel S. .
JOURNAL OF CLINICAL INVESTIGATION, 2016, 126 (07) :2597-2609
[2]   Astrocytes produce CNTF during the remyelination phase of viral-induced spinal cord demyelination to stimulate FGF-2 production [J].
Albrecht, PJ ;
Murtie, JC ;
Ness, JK ;
Redwine, JM ;
Enterline, JR ;
Armstrong, RC ;
Levison, SW .
NEUROBIOLOGY OF DISEASE, 2003, 13 (02) :89-101
[3]   Insufficient OPC migration into demyelinated lesions is a cause of poor remyelination in MS and mouse models [J].
Boyd, Amanda ;
Zhang, Hui ;
Williams, Anna .
ACTA NEUROPATHOLOGICA, 2013, 125 (06) :841-859
[4]   Defective cholesterol clearance limits remyelination in the aged central nervous system [J].
Cantuti-Castelvetri, Ludovico ;
Fitzner, Dirk ;
Bosch-Queralt, Mar ;
Weil, Marie-Theres ;
Su, Minhui ;
Sen, Paromita ;
Ruhwedel, Torben ;
Mitkovski, Miso ;
Trendelenburg, George ;
Luetjohann, Dieter ;
Moebius, Wiebke ;
Simons, Mikael .
SCIENCE, 2018, 359 (6376) :684-688
[5]   Disease-Modifying Treatment in Progressive Multiple Sclerosis [J].
Ciotti, John Robert ;
Cross, Anne Haney .
CURRENT TREATMENT OPTIONS IN NEUROLOGY, 2018, 20 (05)
[6]   Normal aging induces A1-like astrocyte reactivity [J].
Clarke, Laura E. ;
Liddelow, Shane A. ;
Chakraborty, Chandrani ;
Munch, Alexandra E. ;
Heiman, Myriam ;
Barres, Ben A. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2018, 115 (08) :E1896-E1905
[7]   Multiple sclerosis [J].
Compston, Alastair ;
Coles, Alasdair .
LANCET, 2008, 372 (9648) :1502-1517
[8]   Age at disability milestones in multiple sclerosis [J].
Confavreux, C ;
Vukusic, S .
BRAIN, 2006, 129 :595-605
[9]   Developmental Origin of Oligodendrocyte Lineage Cells Determines Response to Demyelination and Susceptibility to Age-Associated Functional Decline [J].
Crawford, Abbe H. ;
Tripathi, Richa B. ;
Richardson, William D. ;
Franklin, Robin J. M. .
CELL REPORTS, 2016, 15 (04) :761-773
[10]   Pre-Existing Mature Oligodendrocytes Do Not Contribute to Remyelination following Toxin-Induced Spinal Cord Demyelination [J].
Crawford, Abbe H. ;
Tripathi, Richa B. ;
Foerster, Sarah ;
McKenzie, Ian ;
Kougioumtzidou, Eleni ;
Grist, Matthew ;
Richardson, William D. ;
Franklin, Robin J. M. .
AMERICAN JOURNAL OF PATHOLOGY, 2016, 186 (03) :511-516