Advances in molecular therapies for targeting pathophysiology in spinal cord injury

被引:14
作者
Kim, Ha Neui [1 ]
McCrea, Madeline R. [1 ]
Li, Shuxin [1 ]
机构
[1] Temple Univ, Shriners Hosp, Dept Neural Sci, Lewis Katz Sch Med,Pediat Res Ctr, Philadelphia, PA 19140 USA
基金
美国国家卫生研究院;
关键词
Spinal cord injury; treatment; neuroprotection; cell death; neuronal regeneration; neural repair; functional recovery; PROMOTES AXON REGENERATION; IMPROVES FUNCTIONAL RECOVERY; CORTICOSPINAL TRACT AXONS; ACETYL-L-CARNITINE; KETOGENIC DIET; INHIBITING APOPTOSIS; NEURAL REGENERATION; MOTOR RECOVERY; MULLER GLIA; CELL-DEATH;
D O I
10.1080/14728222.2023.2194532
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
IntroductionSpinal cord injury (SCI) affects 25,000-50,000 people around the world each year and there is no cure for SCI patients currently. The primary injury damages spinal cord tissues and secondary injury mechanisms, including ischemia, apoptosis, inflammation, and astrogliosis, further exacerbate the lesions to the spinal cord. Recently, researchers have designed various therapeutic approaches for SCI by targeting its major cellular or molecular pathophysiology.Areas coveredSome strategies have shown promise in repairing injured spinal cord for functional recoveries, such as administering neuroprotective reagents, targeting specific genes to promote robust axon regeneration of disconnected spinal fiber tracts, targeting epigenetic factors to enhance cell survival and neural repair, and facilitating neuronal relay pathways and neuroplasticity for restoration of function after SCI. This review focuses on the major advances in preclinical molecular therapies for SCI reported in recent years.Expert opinionRecent progress in developing novel and effective repairing strategies for SCI is encouraging, but many challenges remain for future design of effective treatments, including developing highly effective neuroprotectants for early interventions, stimulating robust neuronal regeneration with functional synaptic reconnections among disconnected neurons, maximizing the recovery of lost neural functions with combination strategies, and translating the most promising therapies into human use.
引用
收藏
页码:171 / 187
页数:17
相关论文
共 175 条
  • [11] Activation of MAP2K signaling by genetic engineering or HF-rTMS promotes corticospinal axon sprouting and functional regeneration
    Boato, Francesco
    Guan, Xiaofei
    Zhu, Yanjie
    Ryu, Youngjae
    Voutounou, Mariel
    Rynne, Christopher
    Freschlin, Chase R.
    Zumbo, Paul
    Betel, Doron
    Matho, Katie
    Makarov, Sergey N.
    Wu, Zhuhao
    Son, Young-Jin
    Nummenmaa, Aapo
    Huang, Josh Z.
    Edwards, Dylan J.
    Zhong, Jian
    [J]. SCIENCE TRANSLATIONAL MEDICINE, 2023, 15 (677)
  • [12] Poly(ADP-ribose) polymerase 1 is a novel target to promote axonal regeneration
    Brochier, Camille
    Jones, James I.
    Willis, Dianna E.
    Langley, Brett
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (49) : 15220 - 15225
  • [13] Inhibiting poly(ADP-ribosylation) mproves axon regeneration
    Byrne, Alexandra B.
    McWhirter, Rebecca D.
    Sekine, Yuichi
    Strittmatter, Stephen M.
    Miller, David M., III
    Hammarlund, Marc
    [J]. ELIFE, 2016, 5
  • [14] Silencing of Long Noncoding RNA Growth Arrest-Specific 5 Alleviates Neuronal Cell Apoptosis and Inflammatory Responses Through Sponging microRNA-93 to Repress PTEN Expression in Spinal Cord Injury
    Cao, Yuanwu
    Jiang, Chang
    Lin, Haodong
    Chen, Zixian
    [J]. FRONTIERS IN CELLULAR NEUROSCIENCE, 2021, 15
  • [15] Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury
    Casha, Steven
    Zygun, David
    McGowan, M. Dan
    Bains, Ish
    Yong, V. Wee
    Hurlbert, R. John
    [J]. BRAIN, 2012, 135 : 1224 - 1236
  • [16] BET protein inhibition promotes non-myeloid cell mediated neuroprotection after rodent spinal cord contusion
    Cerqueira, Susana R.
    Benavides, Sofia
    Lee, Ha Eun
    Ayad, Nagi G.
    Lee, Jae K.
    [J]. EXPERIMENTAL NEUROLOGY, 2022, 352
  • [17] Exosomes derived from miR-26a-modified MSCs promote axonal regeneration via the PTEN/AKT/mTOR pathway following spinal cord injury
    Chen, Yuyong
    Tian, Zhenming
    He, Lei
    Liu, Can
    Wang, Nangxiang
    Rong, Limin
    Liu, Bin
    [J]. STEM CELL RESEARCH & THERAPY, 2021, 12 (01)
  • [18] MiR-92b-3p promotes neurite growth and functional recovery via the PTEN/AKT pathway in acute spinal cord injury
    Chen, Zixian
    Li, Zheng
    Jiang, Chang
    Jiang, Xiaoxing
    Zhang, Jian
    [J]. JOURNAL OF CELLULAR PHYSIOLOGY, 2019, 234 (12) : 23043 - 23052
  • [19] Respiratory axon regeneration in the chronically injured spinal cord
    Cheng, Lan
    Sami, Armin
    Ghosh, Biswarup
    Goudsward, Hannah J.
    Smith, George M.
    Wright, Megan C.
    Li, Shuxin
    Lepore, Angelo C.
    [J]. NEUROBIOLOGY OF DISEASE, 2021, 155
  • [20] Transcription factor network analysis identifies REST/NRSF as an intrinsic regulator of CNS regeneration in mice
    Cheng, Yuyan
    Yin, Yuqin
    Zhang, Alice
    Bernstein, Alexander M.
    Kawaguchi, Riki
    Gao, Kun
    Potter, Kyra
    Gilbert, Hui-Ya
    Ao, Yan
    Ou, Jing
    Fricano-Kugler, Catherine J.
    Goldberg, Jeffrey L.
    He, Zhigang
    Woolf, Clifford J.
    Sofroniew, Michael V.
    Benowitz, Larry I.
    Geschwind, Daniel H.
    [J]. NATURE COMMUNICATIONS, 2022, 13 (01)