[PDF][PDF] Calcium influx through plasma-membrane nanoruptures drives axon degeneration in a model of multiple sclerosis
ME Witte, AM Schumacher, CF Mahler, JP Bewersdorf… - Neuron, 2019 - cell.com
ME Witte, AM Schumacher, CF Mahler, JP Bewersdorf, J Lehmitz, A Scheiter, P Sanchez…
Neuron, 2019•cell.comAxon loss determines persistent disability in multiple sclerosis patients. Here, we use in vivo
calcium imaging in a multiple sclerosis model to show that cytoplasmic calcium levels
determine the choice between axon loss and survival. We rule out the endoplasmic
reticulum, glutamate excitotoxicity, and the reversal of the sodium-calcium exchanger as
sources of intra-axonal calcium accumulation and instead identify nanoscale ruptures of the
axonal plasma membrane as the critical path of calcium entry.
calcium imaging in a multiple sclerosis model to show that cytoplasmic calcium levels
determine the choice between axon loss and survival. We rule out the endoplasmic
reticulum, glutamate excitotoxicity, and the reversal of the sodium-calcium exchanger as
sources of intra-axonal calcium accumulation and instead identify nanoscale ruptures of the
axonal plasma membrane as the critical path of calcium entry.
Summary
Axon loss determines persistent disability in multiple sclerosis patients. Here, we use in vivo calcium imaging in a multiple sclerosis model to show that cytoplasmic calcium levels determine the choice between axon loss and survival. We rule out the endoplasmic reticulum, glutamate excitotoxicity, and the reversal of the sodium-calcium exchanger as sources of intra-axonal calcium accumulation and instead identify nanoscale ruptures of the axonal plasma membrane as the critical path of calcium entry.
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