The Study Of The Abnormality Neurofilament In Immune-mediated Motor Neuron Injury

Amyotrophic lateral sclerosis (ALS) is an adult-onset and heterogeneous neurological disorder that affects primarily motor neuron of brain stem and spinal cord, resulting in paralysis and death within 3-5years. Although most cases of ALS are sporadic(sALS), 10% are familial (fALS) and, of these, 20% are caused by mutations within the gene encoding the metalloenzyme Cu/Zn superoxide dismutase-1(SOD1). The pathological mechanisms that cause selective motoneuron degeneration in ALS remain unknown for the vast majority of sporadic and familial cases. Many hypotheses have been proposed about the aetiology of the disease, including excitotoxicity, oxdative stress, protein aggregation affecting cytosckeletal function, impaired calcium homeostasis, neurotrophic deficit, and autoimmunity. While the final proof is still lacking, some of these hypothesized mechanism may represent different points of entry into pathway leading to motor neuron degeneraiton. Many evidences lend support to the autoimmunity hypothesis in the previous studies, such as the presence of activeted T-lymphocytes and deposits of immunoglobulins in the anterior horn cells of patient with ALS, and of antibodies that bind and alter the function of L-type and P-type as well as other neuronal calcium-channal, and can induce apoptotic cell death in motoneuron cell line. IgG from ALS patients transferred to mice is taken up in the spinal motor neuron of the recipients. It increases the frequency of miniature end-plate potentials reflecting enhanced acetylcholine release from the motor axon terminals. Passively transferred immunoglobulins from ALS patients also raise the level of glutamate in the cerebrospinal fluid of rats. In a recent study, Engelhardt et al found that immunoglobulins G (IgG) samples isolated from the sera of ALS were injected into mice, the injected ALS IgG was observed in axon terminals of low motor neurons, localized to the...