On my last nerve

A common pathologic feature of many neurodegenerative disorders is loss of the thin myelin sheath that covers the nerve fibers.

Randall C Willis
NEW YORK—A common pathologic feature of many neurodegenerative disorders is loss of the thin myelin sheath that covers the nerve fibers. The ability to stop or reverse this process would go a long way to reversing the debilitating effects of disease like multiple sclerosis. Recently, researchers at Rockefeller University came one step closer to this goal, finding they could reverse demyelination induced by leprosy infection in mice. They presented their work in Nature Medicine.
 
When Mycobacterium leprae, the organism that triggers leprosy, attaches to Schwann cells, it triggers a signal cascade that eventually leads to myelin loss. Using a series of signaling inhibitors in vitro and immunoblots, the researchers noted that the microbe did not interact with the expected surface receptor (laminin-2), but instead with ErbB2, a receptor tyrosine kinase involved in functions like cell proliferation.
 
They tested the impact of ErbB2 kinase inhibitor PKI 166 in cell culture and noted that the small-molecule drug significantly inhibited M. leprae-induced ErbB2 phosphorylation and greatly reduced myelin damage. The drug was then tested in a mouse model of non-immune mediated demyelination. While untreated mice infected with M. leprae exhibited significant demyelination, those given PKI 166 showed reduced demyelination.
 
On the basis of these results, the researchers suggest that therapeutic interventions targeting ErbB2 or other receptor tyrosine kinases might offer potential benefits in limiting the impact of demyelinating neurodegenerative conditions.

Randall C Willis

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