Studies of specific treatment strategies utilizing axoplasmic transpot in motor neuron diseases.

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In order to investigate the possibility of treating the patients with amyotrophic lateral sclerosis, utilizing the phenomenon of retrograde axoplasmic transport, intrinsic transport mechanism was initially studied. This study clarified the somatic motor neurons residing in the spinal anterior horn physiologically take up serum albumin and IgG by way of retrograde axoplasmic transport from the neuromuscular junction. Extracellular matrix forming the neuromuscular junction was then thought to play a role in subserving the reservoir for initial uptake, constituent proteins of the extracellular matrix were examined. Laminin, one of major proteins of the matrix, is known to possess many functional domains, one of which is a potent neurotrophic actions. When motor neurons were immunocytochemically studies with anti-laminin antibody, there was a distinct immunoreactivity in motor neurons. Western blot of the brain homogenates in rat and human disclosed l9OkDalton protein which shares the antigenicity with authentic laminin was found. When the laminin in the CNS (neurolaminin) was compared to authentic laminin, it was found that neurolaminin did not possess subunits under reducing condition and the molecular weight is close to laminin B chain. However, heparin-binding domain appeared not present in neurolaminin, when heparin-affinity column was used. Similarly, neurolaminin did not appear to be an extracellular metric constituent but intra cellular molecule. The study is in progress in order to purify neurolaminin and to see the biological activities which are assumed to be present in this particular molecule. If indeed neurolaminin possesses neurotrophic activity this molecule might be the one which is worthwhile trying to treat the patients with amyotrophic lateral sclerosis, by way of retrograde axoplasmic transport system.