Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 2 of 2
Full-Text Articles in Medicine and Health Sciences
Ephrinb2 Knockdown In Cervical Spinal Cord Preserves Diaphragm Innervation In A Mutant Sod1 Mouse Model Of Als, Mark W. Urban, Brittany A. Charsar, Nicolette M. Heinsinger, Shashirekha S. Markandaiah, Lindsay Sprimont, Wei Zhou, Eric V. Brown, Nathan T. Henderson, Samantha J. Thomas, Biswarup Ghosh, Rachel E. Cain, Davide Trotti, Piera Pasinelli, Megan C. Wright, Matthew B. Dalva, Angelo C. Lepore
Ephrinb2 Knockdown In Cervical Spinal Cord Preserves Diaphragm Innervation In A Mutant Sod1 Mouse Model Of Als, Mark W. Urban, Brittany A. Charsar, Nicolette M. Heinsinger, Shashirekha S. Markandaiah, Lindsay Sprimont, Wei Zhou, Eric V. Brown, Nathan T. Henderson, Samantha J. Thomas, Biswarup Ghosh, Rachel E. Cain, Davide Trotti, Piera Pasinelli, Megan C. Wright, Matthew B. Dalva, Angelo C. Lepore
Farber Institute for Neuroscience Staff Papers and Presentations
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss. Importantly, non-neuronal cell types such as astrocytes also play significant roles in disease pathogenesis. However, mechanisms of astrocyte contribution to ALS remain incompletely understood. Astrocyte involvement suggests that transcellular signaling may play a role in disease. We examined contribution of transmembrane signaling molecule ephrinB2 to ALS pathogenesis, in particular its role in driving motor neuron damage by spinal cord astrocytes. In symptomatic SOD1G93A mice (a well-established ALS model), ephrinB2 expression was dramatically increased in ventral horn astrocytes. Reducing ephrinB2 in the cervical spinal cord ventral horn via …
A Structurally Precise Mechanism Links An Epilepsy-Associated Kcnc2 Potassium Channel Mutation To Interneuron Dysfunction, Jerome Clatot, Christopher B. Currin, Qiansheng Liang, Tanadet Pipatpolkai, Shavonne L. Massey, Ingo Helbig, Lucie Delemotte, Tim P. Vogels, Manuel Covarrubias, Ethan M. Goldberg
A Structurally Precise Mechanism Links An Epilepsy-Associated Kcnc2 Potassium Channel Mutation To Interneuron Dysfunction, Jerome Clatot, Christopher B. Currin, Qiansheng Liang, Tanadet Pipatpolkai, Shavonne L. Massey, Ingo Helbig, Lucie Delemotte, Tim P. Vogels, Manuel Covarrubias, Ethan M. Goldberg
Farber Institute for Neuroscience Staff Papers and Presentations
De novo heterozygous variants in KCNC2 encoding the voltage-gated potassium (K+) channel subunit Kv3.2 are a recently described cause of developmental and epileptic encephalopathy (DEE). A de novo variant in KCNC2 c.374G > A (p.Cys125Tyr) was identified via exome sequencing in a patient with DEE. Relative to wild-type Kv3.2, Kv3.2-p.Cys125Tyr induces K+ currents exhibiting a large hyperpolarizing shift in the voltage dependence of activation, accelerated activation, and delayed deactivation consistent with a relative stabilization of the open conformation, along with increased current density. Leveraging the cryogenic electron microscopy (cryo-EM) structure of Kv3.1, molecular dynamic simulations suggest that a strong π-π stacking …