Researchers Find Protein Determines Nerve’s Fate

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Researchers Find Protein Determines Nerve's Fate

http://www.neuropathy.org/site/PageServer?pagename=ProteinFound

Researchers at the Skirball Institute of Biomolecular Medicine, New

York University (NYU) School of Medicine, have found that a protein

(neuregulin-1 type III, or NRG1-III) essential for the protective

wrapping around a nerve's central wiring, or axons, also determines

its fate.

Just as plastic coatings insulate electrical wires, myelin coats

nerve fibers. This fatty substance also accelerates message-carrying

impulses that travel along the nerve fibers and frees them from

interference. For more than a decade, scientists have known that

nerve cells make neuregulins, growth proteins that promote glial cell

growth. However, the delicate interaction between nerve cells and the

glial cells (Schwann cells) that produce them remain a mystery.

Note: The Neuropathy Association has supported research grants the

work of Dr. Zarife Sahenk, Director of Neuromuscular Diseases at Ohio

State University, on the nerve regeneration effects of the growth

factor protein NT-3 (neurotrophin-3).

It has been shown that growth factor protein NRG1-III triggers glial

cells to make myelin. This knowledge should lead researchers to

develop more effective treatments for several neurological diseases,

including peripheral neuropathy.

To determine that NRG1-III is necessary for myelin production, the

NYU research team grew two cell types together in lab dishes. The mix

of unmyelinated nerve cells from embryonic mice, cells that don't

produce NRG1-III, and glial cells from adult rats showed no

myelination. However, when the nerve cells were altered genetically

to produce and release NRG1-III, the glial cells quickly coated them

with protective myelin.

The NYU research team reported in the September 2005 issue of Neuron

magazine that the amount of NRG1-III produced by a newly developed

nerve cell is directly related to the thickness of the protective

myelin sheath provided by glial cells. The team found that the

sensory neurons in mice deficient in NRG1-III are poorly sheathed and

fail to myelinate. That strongly suggests that nerve cells are

significant in determining their own fate.

The team also discovered that lentiviral-mediated expression of NRG1-

III rescues these defects and myelinates the axons of sympathetic

neurons. Nerve fibers extending from these neurons are also

disproportionately unmyelinated, aberrantly sheathed, and

hypomyelinated, with reduced conduction velocities.

Members of the NYU team are C. Taveggia, G. Zanazzi, A. Petrylak, H.

Yano, J. Rosenbluth. S. Einheber, X. Xu, R. M. Esper, J. A. Loeb, P.

Shrager, M. V. Chao, D. L. Falls, L. Role L and J. L. Salzer.