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Biological Chemistry

Blocking Protein Transport Protects Neurons

by Michael Torrice
March 9, 2015 | A version of this story appeared in Volume 93, Issue 10

Some scientists think the neuronal damage that results from some neurodegenerative diseases is linked to improper trafficking of proteins around the nerve cell. A study now shows that inhibiting a transporter protein that shuttles cargo from the nucleus into the cytoplasm can relieve multiple-sclerosis-like symptoms in mice, suggesting a possible new treatment strategy (Nat. Neurosci. 2015, DOI: 10.1038/nn.3953). A team including Jeffery D. Haines and Patrizia Casaccia of the Icahn School of Medicine at Mount Sinai, in New York City, previously connected neuronal damage in mice to increased export of a histone deacetylase from the nuclei of nerve cells. In the new study, the scientists tested two inhibitors of a nuclear transporter protein, called CRM1, on affected mice that already exhibited paralysis in their hind limbs. Untreated mice continued to develop full paralysis, whereas those given the inhibitors improved, with some paralysis being reversed. Further experiments suggested that the inhibitors may relieve symptoms by protecting against neuronal damage and by modulating immune cell activity. The inhibitors were synthesized by Karyopharm Therapeutics, which has started preclinical testing on one inhibitor, KPT-350, for treating autoimmune diseases.

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