Intrinsic Membrane Hyperexcitability of Amyotrophic Lateral Sclerosis Patient-Derived Motor Neurons
Boston Children's Hospital · Massachusetts General Hospital · +5 more institutions
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the motor nervous system. We show using multielectrode array and patch-clamp recordings that hyperexcitability detected by clinical neurophysiological studies of ALS patients is recapitulated in induced pluripotent stem cell-derived motor neurons from ALS patients harboring superoxide dismutase 1 (SOD1), C9orf72, and fused-in-sarcoma mutations. Motor neurons produced from a genetically corrected but otherwise isogenic SOD1(+/+) stem cell line do not display the hyperexcitability phenotype. SOD1(A4V/+) ALS patient-derived motor neurons have reduced delayed-rectifier potassium current amplitudes relative to control-derived motor neurons,…
Citation impact
- FWCI
- 45.31
- Percentile
- 100%
- References
- 49
Authors
16- BJBrian J. Wainger
Boston Children's Hospital, Massachusetts General Hospital, Harvard Stem Cell Institute
- EKEvangelos Kiskinis
Broad Institute, Harvard University, Harvard Stem Cell Institute
- CMCassidy Mellin
Boston Children's Hospital, Harvard Stem Cell Institute
- OWOle Wiskow
Broad Institute, Harvard University, Harvard Stem Cell Institute
- SSSteve S.W. Han
Broad Institute, Harvard University, Massachusetts General Hospital, Harvard Stem Cell Institute
Topics & keywords
- Amyotrophic lateral sclerosis
- Neuroscience
- Motor neuron
- Multiple sclerosis
- Medicine
- Chemistry
- Biology
- Pathology
- Good health and well-being