Editors' ChoiceNeuroscience

Hypothermia-induced neuroprotection

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Science Signaling  14 Mar 2017:
Vol. 10, Issue 470, eaan1410
DOI: 10.1126/scisignal.aan1410

A reticulon contributes to the neuroprotective effects of hypothermia.

Therapeutic hypothermia improves the clinical outcome for some patients who have experienced ischemic or traumatic brain injury. One of the proteins that mediates hypothermia-induced neuroprotection is the RNA-binding protein RBM3, which accumulates in response to cold shock. Overexpression of RBM3 in the absence of cold shock reduces neurodegeneration and cognitive impairments in mouse models of neurodegenerative disease. Bastide et al. found that although cold shock induced a global reduction in translational elongation in cultured cells, it also stimulated the translation of some transcripts, including those encoding the endoplasmic reticulum (ER) protein reticulon 3 (RTN3). RBM3 bound to RTN3 transcripts and promoted their translation in both cultured cells and in the mouse hippocampus even in the absence of cold shock. Hypothermia stimulated the translation of RTN3 in the hippocampus, and knocking down RTN3 abrogated the neuroprotective effects of cooling in a mouse model of prion disease. Overexpression of RTN3 reduced synapse loss and behavioral phenotypes in these mice in the absence of cooling. In addition to playing a role in the structure and function of the ER, RTN3 also reduces autophagy and inhibits BACE1, a protease that contributes to the deposition of amyloid plaques. Whether these or additional functions are responsible for the neuroprotective effects of RTN3 remains to be determined, but these findings identify RTN3 as a potential target for treating neurodegenerative disease.

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