Neuron-targeted caveolin-1 improves neuromuscular function and extends survival in SOD1G93A mice

FASEB J. 2019 Jun;33(6):7545-7554. doi: 10.1096/fj.201802652RR. Epub 2019 Mar 20.


Interventions that preserve motor neurons or restore functional motor neuroplasticity may extend longevity in amyotrophic lateral sclerosis (ALS). Delivery of neurotrophins may potentially revive degenerating motor neurons, yet this approach is dependent on the proper subcellular localization of neurotrophin receptor (NTR) to plasmalemmal signaling microdomains, termed membrane/lipid rafts (MLRs). We previously showed that overexpression of synapsin-driven caveolin-1 (Cav-1) (SynCav1) increases MLR localization of NTR [e.g., receptor tyrosine kinase B (TrkB)], promotes hippocampal synaptic and neuroplasticity, and significantly improves learning and memory in aged mice. The present study crossed a SynCav1 transgene-positive (SynCav1+) mouse with the mutant human superoxide dismutase glycine to alanine point mutation at amino acid 93 (hSOD1G93A) mouse model of ALS. When compared with hSOD1G93A, hSOD1G93A/SynCav1+ mice exhibited greater body weight and longer survival as well as better motor function. Microscopic analyses of hSOD1G93A/SynCav1+ spinal cords revealed preserved spinal cord α-motor neurons and preserved mitochondrial morphology. Moreover, hSOD1G93A/SynCav1+ spinal cords contained more MLRs (cholera toxin subunit B positive) and MLR-associated TrkB and Cav-1 protein expression. These findings demonstrate that SynCav1 delays disease progression in a mouse model of ALS, potentially by preserving or restoring NTR expression and localization to MLRs.-Sawada, A., Wang, S., Jian, M., Leem, J., Wackerbarth, J., Egawa, J., Schilling, J. M., Platoshyn, O., Zemljic-Harpf, A., Roth, D. M., Patel, H. H., Patel, P. M., Marsala, M., Head, B. P. Neuron-targeted caveolin-1 improves neuromuscular function and extends survival in SOD1G93A mice.

Keywords: MLR; TrkB; mitochondria; motor neurons; neuroplasticity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Body Weight
  • Caveolin 1 / metabolism
  • Caveolin 1 / physiology*
  • Electric Stimulation
  • Humans
  • Longevity
  • Male
  • Mice
  • Mice, Transgenic
  • Motor Neurons / cytology
  • Muscle, Skeletal / physiology*
  • Nervous System Physiological Phenomena*
  • Superoxide Dismutase-1 / genetics*
  • Survival Rate


  • Cav1 protein, mouse
  • Caveolin 1
  • Sod1 protein, mouse
  • Superoxide Dismutase-1