The Struggle to Make CNS Axons Regenerate: Why Has It Been so Difficult?

Neurochemical Research
J W Fawcett

Abstract

Axon regeneration in the CNS is inhibited by many extrinsic and intrinsic factors. Because these act in parallel, no single intervention has been sufficient to enable full regeneration of damaged axons in the adult mammalian CNS. In the external environment, NogoA and CSPGs are strongly inhibitory to the regeneration of adult axons. CNS neurons lose intrinsic regenerative ability as they mature: embryonic but not mature neurons can grow axons for long distances when transplanted into the adult CNS, and regeneration fails with maturity in in vitro axotomy models. The causes of this loss of regeneration include partitioning of neurons into axonal and dendritic fields with many growth-related molecules directed specifically to dendrites and excluded from axons, changes in axonal signalling due to changes in expression and localization of receptors and their ligands, changes in local translation of proteins in axons, and changes in cytoskeletal dynamics after injury. Also with neuronal maturation come epigenetic changes in neurons, with many of the transcription factor binding sites that drive axon growth-related genes becoming inaccessible. The overall aim for successful regeneration is to ensure that the right molecules are expre...Continue Reading

References

Sep 1, 1991·Journal of Neuroscience Research·P W BaasM M Black
May 15, 1986·The Journal of Comparative Neurology·P J ReierJ R Wujek
Jan 1, 1994·Progress in Brain Research·W TetzlaffA M Bedard
Dec 17, 1997·Experimental Neurology·H Bernstein-GoralB S Bregman
Dec 14, 1999·The European Journal of Neuroscience·S R SinclairS B Dunnett
Apr 6, 2001·Results and Problems in Cell Differentiation·G J Bassell, R H Singer
Feb 28, 2002·Molecular and Cellular Neurosciences·Matt S RamerStephen B McMahon
May 25, 2004·Nature Medicine·Damien D PearseMary Bartlett Bunge
Jul 23, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Veronica J TomJerry Silver
Jan 14, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Poonam VermaJames W Fawcett
Feb 4, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Karim FouadDamien D Pearse
May 19, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Zixuan CaoMarie T Filbin
Jul 19, 2006·Proceedings of the National Academy of Sciences of the United States of America·Lynda J S YangRonald L Schnaar
Aug 10, 2006·Cellular and Molecular Neurobiology·Dasa CízkováMilan Cízek
Sep 19, 2006·Nature Neuroscience·Kin-Mei LeungChristine E Holt
Oct 21, 2006·Biochemical Society Transactions·P T HawkinsL R Stephens
Nov 3, 2006·Brain Research Reviews·Gennadij Raivich, Milan Makwana
Jun 5, 2007·The Journal of Biological Chemistry·Robert J RomanelliTeresa L Wood
Aug 24, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ali ErtürkFrank Bradke
Feb 1, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Fenghua Hu, Stephen M Strittmatter
Jan 24, 2009·Science·Marc HammarlundMichael Bastiani
Feb 13, 2009·Current Biology : CB·Guillaume MontagnacPhilippe Chavrier
Apr 11, 2009·Proceedings of the National Academy of Sciences of the United States of America·Edmund R HollisMark H Tuszynski

❮ Previous
Next ❯

Citations

Aug 19, 2020·Cells·Roberta Romano, Cecilia Bucci
Sep 24, 2020·International Journal of Molecular Sciences·Pavle AndjusBarbara Zavan
Dec 21, 2019·Neurochemical Research·N Joan AbbottAlexei Verkhratsky
Apr 23, 2020·Frontiers in Molecular Neuroscience·Cristina Roselló-BusquetsRamon Martínez-Mármol
Feb 12, 2021·Developmental Cell·Eitan Erez ZahaviCasper C Hoogenraad
Mar 2, 2021·Neural Regeneration Research·Katherine L Marshall, Mohamed H Farah
Apr 20, 2021·Frontiers in Molecular Biosciences·Matilde GhibaudiAlessandro Vercelli
Jun 21, 2021·Progress in Neurobiology·Leon TeoJames A Bourne
Aug 3, 2021·Acta Biomaterialia·Eleana ManousiouthakisChristine E Schmidt
Dec 29, 2020·Current Opinion in Neurobiology·Sérgio Carvalho LeiteMonica Mendes Sousa

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsies
GTPases
acetylation
histone acetylation

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.