Journal of Molecular Neuroscience

, Volume 43, Issue 3, pp 470–477

The “Dying-Back” Phenomenon of Motor Neurons in ALS


DOI: 10.1007/s12031-010-9467-1

Cite this article as:
Dadon-Nachum, M., Melamed, E. & Offen, D. J Mol Neurosci (2011) 43: 470. doi:10.1007/s12031-010-9467-1


Amyotrophic lateral sclerosis (ALS) is a lethal disease, characterized by progressive death of motor neurons with unknown etiology. Evidence from animal models indicates that neuronal dysfunction precedes the clinical phase of the disease. However, in parallel extensive nerve sprouting and synaptic remodeling as part of a compensatory reinnervation processes and possibly also of motor neurons pathology was demonstrated. Therefore, the weakness in muscle groups will not be clinically apparent until a large proportion of motor units are lost. This motor unit loss and associated muscle function which precedes the death of motor neurons may resemble the “die-back” phenomena. Studies indicated that in the early stages the nerve terminals and motor neuron junctions are partially degraded while the cell bodies in the spinal cord are mostly intact. Treatments to rescue motor neurons according to “dying-forward” model of motor neuron pathology in ALS have shown only limited success in SOD1G93A transgenic mice as well as in humans. If cell body degeneration is late compared with axonal degeneration, early intervention could potentially prevent loss of motor neurons. Therefore, it should be considered, according to the dying back hypothesis, to focus on motor neurons terminals in order to delay or prevent the progressive degradation.


Amyotrophic lateral sclerosisMotor neuronDying back

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Michal Dadon-Nachum
    • 1
    • 2
  • Eldad Melamed
    • 1
    • 2
  • Daniel Offen
    • 1
    • 2
  1. 1.The Neuroscience Laboratory, Felsenstein Medical Research CenterRabin Medical CenterPetah TikvaIsrael
  2. 2.Sackler School of MedicineTel-Aviv UniversityTel AvivIsrael