IGF-1R Reduction Triggers Neuroprotective Signaling Pathways in Spinal Muscular Atrophy Mice.
Olivier BiondiJulien BranchuAmina Ben SalahLéo HoudebineLise BertinFarah ChaliCéline DesseilleLaure WeillGabriel SanchezCamille LancelinSaba AïdPhilippe LopesClaude ParisetSylvie LécolleJocelyn CôtéMartin HolzenbergerChristophe ChanoineCharbel MassaadFrédéric CharbonnierPublished in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2015)
Recent evidence of IGF-1 axis alteration in spinal muscular atrophy (SMA), a very severe neurodegenerative disease affecting specifically the motor neurons, have triggered a renewed interest in insulin-like growth factor-1 (IGF-1) pathway activation as a potential therapeutic approach for motor neuron diseases. The present study challenges this point of view and brings the alternative hypothesis that reducing rather than enhancing the IGF-1 signaling pathway exerts a neuroprotective effect in SMA. Furthermore, the present data substantiate a newly emerging concept that the modulation of IGF-1 receptor expression is a key event selectively determining the activation level of intracellular pathways that lie downstream of the receptor. This aspect should be considered when designing IGF-1-based treatments for neurodegenerative diseases.
Keyphrases
- pi k akt
- signaling pathway
- growth hormone
- binding protein
- cell proliferation
- epithelial mesenchymal transition
- spinal cord
- oxidative stress
- machine learning
- adipose tissue
- early onset
- spinal cord injury
- deep learning
- skeletal muscle
- blood brain barrier
- artificial intelligence
- high fat diet induced
- endoplasmic reticulum stress
- drug induced
- wild type