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Klin Monbl Augenheilkd 2020; 237(02): 128-132
DOI: 10.1055/a-1079-5905
Übersicht
Georg Thieme Verlag KG Stuttgart · New York

Neuroprotektion und Regeneration im Zentralnervensystem

Neuroprotection and Regeneration in the Central Nervous System
Markus Höltje
1   Institut für Integrative Neuroanatomie, Charité – Universitätsmedizin Berlin
,
Francesco Boato
2   Linda van Aelst Lab, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States
› Author Affiliations
Further Information

Publication History

eingereicht 19 November 2019

akzeptiert 02 December 2019

Publication Date:
10 February 2020 (online)

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Zusammenfassung

Die Entwicklung neuroprotektiver und regenerativer Therapieansätze im Zentralnervensystem (ZNS) stellt eine große Herausforderung in der klinischen und grundlagenbasierten Forschung dar. Im Gegensatz zum peripheren Nervensystem, das eine vergleichsweise hohe intrinsische Regenerationsfähigkeit zeigt, ist diese Eigenschaft im adulten ZNS nur schwach ausgeprägt. In dieser Übersichtsarbeit sollen einige grundlegende Wachstumsmechanismen zentralnervöser Neurone beleuchtet werden, ebenso wie Faktoren, die einer erfolgreichen Regeneration nach Schädigung entgegenstehen. Vorwiegend im Kontext der Glaukomerkrankung werden präklinische und klinische Studien vorgestellt, die das Verständnis neurodegenerativer Vorgänge im optischen System verbessern und somit die Grundlagen für aktuelle und zukünftige Therapiestrategien liefern können.

Abstract

The development of neuroprotective and regenerative therapies in the central nervous system (CNS) poses a major challenge in clinical and basic research. In contrast to the peripheral nervous system, which has a comparatively high intrinsic regenerative capacity, this characteristic is poorly developed in the adult CNS. In this review, some basic growth mechanisms of CNS neurons will be highlighted, as well as factors that prevent successful regeneration after injury. Primarily in the context of glaucoma, preclinical and clinical studies are presented which can improve the understanding of neurodegenerative processes in the optical system and thus provide the basis for current and future therapeutic strategies.

Schlüsselwörter

Glaukom - Neuroophthalmologie - Neuroprotektion

Key words

glaucoma - neuroophthalmology - neuroprotection
 

  • Literatur

  • 1 Stenevi U, Bjorklund A, Svendgaard NA. Transplantation of central and peripheral monoamine neurons to the adult rat brain: techniques and conditions for survival. Brain Res 1976; 114: 1-20
    CrossrefPubMedGoogle Scholar
  • 2 Reier PJ, Bregman BS, Wujek JR. Intraspinal transplantation of embryonic spinal cord tissue in neonatal and adult rats. J Comp Neurol 1986; 247: 275-296
    CrossrefPubMedGoogle Scholar
  • 3 Lu P, Kadoya K, Tuszynski MH. Axonal growth and connectivity from neural stem cell grafts in models of spinal cord injury. Curr Opin Neurobiol 2014; 27: 103-109
    CrossrefPubMedGoogle Scholar
  • 4 Koseki H, Donega M, Lam BY. et al. Selective rab11 transport and the intrinsic regenerative ability of CNS axons. Elife 2017; 6: e26956
    CrossrefPubMedGoogle Scholar
  • 5 Andrews MR, Czvitkovich S, Dassie E. et al. Alpha9 integrin promotes neurite outgrowth on tenascin-C and enhances sensory axon regeneration. J Neurosci 2009; 29: 5546-5557
    CrossrefPubMedGoogle Scholar
  • 6 Hollis ER, Jamshidi P, Low K. et al. Induction of corticospinal regeneration by lentiviral trkB-induced Erk activation. Proc Natl Acad Sci U S A 2009; 106: 7215-7220
    CrossrefPubMedGoogle Scholar
  • 7 Eva R, Dassie E, Caswell PT. et al. Rab11 and its effector Rab coupling protein contribute to the trafficking of beta 1 integrins during axon growth in adult dorsal root ganglion neurons and PC12 cells. J Neurosci 2010; 30: 11654-11669
    CrossrefPubMedGoogle Scholar
  • 8 Trakhtenberg EF, Li Y, Feng Q. et al. Zinc chelation and Klf9 knockdown cooperatively promote axon regeneration after optic nerve injury. Exp Neurol 2018; 300: 22-29
    CrossrefPubMedGoogle Scholar
  • 9 Fawcett JW, Schwab ME, Montani L, Brazda N, Müller HW. Defeating inhibition of regeneration by scar and myelin components. Handb Clin Neurol 2012; 109: 503-522
    PubMedGoogle Scholar
  • 10 Kamber D, Erez H, Spira ME. Local calcium-dependent mechanisms determine whether a cut axonal end assembles a retarded endbulb or competent growth cone. Exp Neurol 2009; 219: 112-125
    CrossrefPubMedGoogle Scholar
  • 11 Hilton BJ, Bradke F. Can injured adult CNS axons regenerate by recapitulating development?. Development 2017; 144: 3417-3429
    CrossrefPubMedGoogle Scholar
  • 12 Wang X, Yigitkanli K, Kim CY. et al. Human NgR-Fc decoy protein via lumbar intrathecal bolus administration enhances recovery from rat spinal cord contusion. J Neurotrauma 2014; 31: 1955-1966
    CrossrefPubMedGoogle Scholar
  • 13 Solomon AM, Westbrook T, Field GD. et al. Nogo receptor 1 is expressed by nearly all retinal ganglion cells. PLoS One 2018; 13: e0196565
    CrossrefPubMedGoogle Scholar
  • 14 Su Y, Wang F, Teng Y. et al. Axonal regeneration of optic nerve after crush in Nogo66 receptor knockout mice. Neurosci Lett 2009; 460: 223-226
    CrossrefPubMedGoogle Scholar
  • 15 Mdzomba JB, Jordi N, Rodriguez L. et al. Nogo-A inactivation improves visual plasticity and recovery after retinal injury. Cell Death Dis 2018; 9: 727
    CrossrefPubMedGoogle Scholar
  • 16 Aktories K, Frevert J. ADP-ribosylation of a 21–24 kDa eukaryotic protein(s) by C3, a novel botulinum ADP-ribosyltransferase, is regulated by guanine nucleotide. Biochem J 1987; 247: 363-368
    CrossrefPubMedGoogle Scholar
  • 17 Fehlings MG, Kim KD, Aarabi B. et al. Rho Inhibitor VX-210 in acute traumatic subaxial cervical spinal cord injury: design of the SPinal cord injury Rho INhibition investiGation (SPRING) clinical trial. J Neurotrauma 2018; 35: 1049-1056
    CrossrefPubMedGoogle Scholar
  • 18 Lehmann M, Fournier A, Selles-Navarro I. et al. Inactivation of Rho signaling pathway promotes CNS axon regeneration. J Neurosci 1999; 19: 7537-7547
    CrossrefPubMedGoogle Scholar
  • 19 Fischer D, Petkova V, Thanos S. et al. Switching mature retinal ganglion cells to a robust growth state in vivo: gene expression and synergy with RhoA inactivation. J Neurosci 2004; 24: 8726-8740
    CrossrefPubMedGoogle Scholar
  • 20 Boato F, Hendrix S, Huelsenbeck SC. et al. C3 peptide enhances recovery from spinal cord injury by improved regenerative growth of descending fiber tracts. J Cell Sci 2010; 123: 1652-1662
    CrossrefPubMedGoogle Scholar
  • 21 Loske P, Boato F, Hendrix S. et al. Minimal essential length of Clostridium botulinum C3 peptides to enhance neuronal regenerative growth and connectivity in a non-enzymatic mode. J Neurochem 2012; 120: 1084-1096
    PubMedGoogle Scholar
  • 22 Berrino E, Supuran CT. Rho-kinase inhibitors in the management of glaucoma. Expert Opin Ther Pat 2019; 29: 817-827
    CrossrefPubMedGoogle Scholar
  • 23 Tezel G. Oxidative stress in glaucomatous neurodegeneration: mechanisms and consequences. Prog Retin Eye Res 2006; 25: 490-513
    CrossrefPubMedGoogle Scholar
  • 24 Turunen M, Olsson J, Dallner G. Metabolism and function of coenzyme Q. Biochim Biophys Acta 2004; 1660: 171-199
    PubMedGoogle Scholar
  • 25 Lee D, Shim MS, Kim KY. et al. Coenzyme Q10 inhibits glutamate excitotoxicity and oxidative stress-mediated mitochondrial alteration in a mouse model of glaucoma. Invest Ophthalmol Vis Sci 2014; 55: 993-1005
    CrossrefPubMedGoogle Scholar
  • 26 Parisi V, Centofanti M, Gandolfi S. et al. Effects of coenzyme Q10 in conjunction with vitamin E on retinal-evoked and cortical-evoked responses in patients with open-angle glaucoma. J Glaucoma 2014; 23: 391-404
    CrossrefPubMedGoogle Scholar
  • 27 Leibinger M, Andreadaki A, Gobrecht P. et al. Boosting central nervous system axon regeneration by circumventing limitations of natural cytokine signaling. Mol Ther 2016; 24: 1712-1725
    CrossrefPubMedGoogle Scholar
  • 28 Lingor P, Tönges L, Pieper N. et al. ROCK inhibition and CNTF interact on intrinsic signalling pathways and differentially regulate survival and regeneration in retinal ganglion cells. Brain 2008; 131: 250-263
    CrossrefPubMedGoogle Scholar
  • 29 Wilson AM, Di Polo A. Gene therapy for retinal ganglion cell neuroprotection in glaucoma. Gene Ther 2012; 19: 127-136
    PubMedGoogle Scholar
  • 30 Khatib TZ, Martin KR. Protecting retinal ganglion cells. Eye (Lond) 2017; 31: 218-224
    CrossrefPubMedGoogle Scholar
  • 31 Johnson TV, Bull ND, Hunt DP. et al. Neuroprotective effects of intravitreal mesenchymal stem cell transplantation in experimental glaucoma. Invest Ophthalmol Vis Sci 2010; 51: 2051-2059
    CrossrefPubMedGoogle Scholar
  • 32 Venugopalan P, Wang Y, Nguyen T. et al. Transplanted neurons integrate into adult retinas and respond to light. Nat Commun 2016; 7: 10472
    CrossrefPubMedGoogle Scholar
  • 33 Chao JR, Lamba DA, Klesert TR. et al. Transplantation of human embryonic stem cell-derived retinal cells into the subretinal space of a non-human primate. Transl Vis Sci Technol 2017; 6: 4
    PubMedGoogle Scholar
  • 34 Casson RJ, Han G, Ebneter A. et al. Glucose-induced temporary visual recovery in primary open-angle glaucoma: a double-blind, randomized study. Ophthalmology 2014; 121: 1203-1211
    CrossrefPubMedGoogle Scholar