Oligodendroglia and myelin pathology in fragile X syndrome

被引:0
作者
Hourani, Shaima [1 ,2 ,3 ,4 ,5 ]
Pouladi, Mahmoud A. [1 ,2 ,3 ,4 ,5 ,6 ]
机构
[1] Dept Med Genet, Vancouver, BC, Canada
[2] Ctr Mol Med & Therapeut, Vancouver, BC, Canada
[3] Djavad Mowafaghian Ctr Brain Hlth, Vancouver, BC, Canada
[4] Univ British Columbia, Fac Med, Edwin SH Leong Ctr Hlth Aging, Vancouver, BC, Canada
[5] British Columbia Childrens Hosp, Res Inst, Vancouver, BC, Canada
[6] Univ British Columbia, Fac Med, Dept Med Genet, Vancouver, BC, Canada
关键词
fragile X messenger ribonucleoprotein 1 (FMRP); fragile X syndrome (FXS); myelination; oligodendrocytes; RNA-binding protein; white matter (WM); CILIARY NEUROTROPHIC FACTOR; MENTAL-RETARDATION PROTEIN; WHITE-MATTER; MOUSE MODEL; MINOCYCLINE TREATMENT; MESSENGER-RNA; SPINAL-CORD; ABNORMALITIES; TRANSLATION; EXPRESSION;
D O I
10.1111/jnc.16144
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Studies of the pathophysiology of fragile X syndrome (FXS) have predominantly focused on synaptic and neuronal disruptions in the disease. However, emerging studies highlight the consistency of white matter abnormalities in the disorder. Recent investigations using animal models of FXS have suggested a role for the fragile X translational regulator 1 protein (FMRP) in the development and function of oligodendrocytes, the myelinating cells of the central nervous system. These studies are starting to uncover FMRP's involvement in the regulation of myelin-related genes, such as myelin basic protein, and its influence on the maturation and functionality of oligodendrocyte precursor cells and oligodendrocytes. Here, we consider evidence of white matter abnormalities in FXS, review our current understanding of FMRP's role in oligodendrocyte development and function, and highlight gaps in our knowledge of the pathogenic mechanisms that may contribute to white matter abnormalities in FXS. Addressing these gaps may help identify new therapeutic strategies aimed at enhancing outcomes for individuals affected by FXS.image The review article by Hourani and Pouladi explores how oligodendrocytes and the myelin they produce are implicated in fragile X syndrome (FXS), a major genetic cause of intellectual disability and autism. While most research on FXS has focused on how neurons are affected, this review highlights the notable alterations in brain white matter in FXS individuals and animal models. It discusses the role of Fragile X Messenger Ribonucleoprotein 1 (FMRP), whose loss causes FXS, in oligodendrocyte development and function, exploring potential mechanisms of oligodendroglial dysfunction as well as new research directions that could pave the way for innovative treatments.image
引用
收藏
页码:2214 / 2226
页数:13
相关论文
共 92 条
  • [31] Neuronal activity biases axon selection for myelination in vivo
    Hines, Jacob H.
    Ravanelli, Andrew M.
    Schwindt, Rani
    Scott, Ethan K.
    Appel, Bruce
    [J]. NATURE NEUROSCIENCE, 2015, 18 (05) : 683 - +
  • [32] Astrocytic Contributions to Synaptic and Learning Abnormalities in a Mouse Model of Fragile X Syndrome
    Hodges, Jennifer L.
    Yu, Xinzhu
    Gilmore, Anthony
    Bennett, Hannah
    Tjia, Michelle
    Perna, James F.
    Chen, Chia-Chien
    Li, Xiang
    Lu, Ju
    Zuo, Yi
    [J]. BIOLOGICAL PSYCHIATRY, 2017, 82 (02) : 139 - 149
  • [33] Altered mTOR signaling and enhanced CYFIP2 expression levels in subjects with fragile X syndrome
    Hoeffer, C. A.
    Sanchez, E.
    Hagerman, R. J.
    Mu, Y.
    Nguyen, D. V.
    Wong, H.
    Whelan, A. M.
    Zukin, R. S.
    Klann, E.
    Tassone, F.
    [J]. GENES BRAIN AND BEHAVIOR, 2012, 11 (03) : 332 - 341
  • [34] Morphometric spatial patterns differentiating boys with fragile X syndrome, typically developing boys, and developmentally delayed boys aged 1 to 3 years
    Hoeft, Fumiko
    Lightbody, Amy A.
    Hazlett, Heather Cody
    Patnaik, Swetapadma
    Piven, Joseph
    Reiss, Allan L.
    [J]. ARCHIVES OF GENERAL PSYCHIATRY, 2008, 65 (09) : 1087 - 1097
  • [35] Neuroanatomical Differences in Toddler Boys With Fragile X Syndrome and Idiopathic Autism
    Hoeft, Fumiko
    Walter, Elizabeth
    Lightbody, Amy A.
    Hazlett, Heather C.
    Chang, Catie
    Piven, Joseph
    Reiss, Allan L.
    [J]. ARCHIVES OF GENERAL PSYCHIATRY, 2011, 68 (03) : 295 - 305
  • [36] Region-specific alterations in brain development in one- to three-year-old boys with fragile X syndrome
    Hoeft, Fumiko
    Carter, John C.
    Lightbody, Amy A.
    Hazlett, Heather Cody
    Piven, Joseph
    Reiss, Allan L.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (20) : 9335 - 9339
  • [37] Astrocytes promote myelination in response to electrical impulses
    Ishibashi, T
    Dakin, KA
    Stevens, B
    Lee, PR
    Kozlov, SV
    Stewart, CL
    Fields, RD
    [J]. NEURON, 2006, 49 (06) : 823 - 832
  • [38] White-Matter Repair as a Novel Therapeutic Target for Early Adversity
    Islam, Rafiad
    Kaffman, Arie
    [J]. FRONTIERS IN NEUROSCIENCE, 2021, 15
  • [39] The Fragile X Mental Retardation Protein Regulates Matrix Metalloproteinase 9 mRNA at Synapses
    Janusz, Aleksandra
    Milek, Jacek
    Perycz, Malgorzata
    Pacini, Laura
    Bagni, Claudia
    Kaczmarek, Leszek
    Dziembowska, Magdalena
    [J]. JOURNAL OF NEUROSCIENCE, 2013, 33 (46) : 18234 - 18241
  • [40] Altered Translational Control of Fragile X Mental Retardation Protein on Myelin Proteins in Neuropsychiatric Disorders
    Jeon, Se Jin
    Ryu, Jong Hoon
    Bahn, Geon Ho
    [J]. BIOMOLECULES & THERAPEUTICS, 2017, 25 (03) : 231 - 238