Scientists at the University of Glasgow have found that both mouse and human GMI-specific antibodies can damage live mouse nerve cells. These antibodies were previously only associated with neuropathy.
Initial analysis indicated that only some mouse GM1-specific antibodies could bind and damage the nerve cells. With further examination, the team discovered that the other antibodies were unable to bind and damage liver mouse cells because the part of GM1 to which they bind was blocked by other ganglioside molecules on the nerve cell surface. Once the cells were treated to remove the blocking ganglioside molecules, the antibodies bound GM1 and damaged the live mouse nerve cells.
Investigators exposed the cryptic GM1 binding domain using a sialidase treatment that released sialic acid from masking gangliosides such as GD1a and by disrupting the live membrane via fixation or freezing. The antibodies damaged living terminal motor axons, blocking synaptic transmission.
Similar hidden binding sites on GM1 were identified for human GM1-specific antibodies, which helps explain why scientists have been unsure about whether the GM1-specific antibodies cause neuropathy.
The article appears in the February 16 online edition of the Journal of Clinical Investigation.
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