Security breach: peripheral nerves provide unrestricted access for toxin delivery into the central nervous system.

We explore the hypothesis that a potential explanation for the initiation of motor neuron disease is an unappreciated vulnerability in central nervous system defense, the direct delivery of neurotoxins into motor neurons via peripheral nerve retrograde transport. This further suggests a mechanism for focal initiation of neuro-degenerative diseases in general, with subsequent spread by network degeneration as suggested by the Frost-Diamond hypothesis. We propose this vulnerability may be a byproduct of vertebrate evolution in a benign aquatic environment, where external surfaces were not exposed to concentrated neurotoxins.