Huperzine a Protects Motor Neurons in an Organotypic Spinal Cord Culture Model of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (Amyotrophic Lateral Sclerosis, ALS) is selectively involving chronic progressive degenerative disease of the lower motor neuron. It is based on a progressive muscle weakness fatal disease characterized many patients at the first symptoms after 3-5 years, died of respiratory failure. ALS pathogenesis may be focused on the following aspects: 1) Cu / Zn SOD gene mutation; 2) glutamate excitotoxicity; 3) mitochondrial dysfunction; 4) oxidative stress; 5) virus infection; 6 ) immune abnormalities. The glutamate excitotoxicity role sporadic amyotrophic lateral sclerosis (Sporadic Amyotrophic Lateral Sclerosis SALS) important in the pathogenesis of glutamate transporter function was significantly inhibited in pathological cases, extracellular glutamate concentration abnormal increase to hyperstimulation its receptor excitotoxic effect on the central nervous system. In vitro (or organization) cultured spinal cord organotypic culture occupies an important place in the study of ALS. Spinal cord organotypic culture, the culture can survive for more than three months, the synaptic connections between good cell morphology and cell-cell can be demonstrated. ALS spinal cord organ culture model as an in vitro study of ALS, it is the use of spinal cord organotypic culture glutamate transporter inhibitor added to the culture medium, inhibition of glutamate transporter, resulting in the synaptic cleft Valley acid concentration increased, according to the mechanism of glutamate excitotoxicity, damage the motor neurons in the ventral horn. It can serve as a good model to study the neuroprotective effects of drugs, the use of certain drugs for preclinical provide an important experimental basis for the treatment of ALS. ALS is very difficult to treat, the ALS drug research including excitatory amino acid antagonists, neurotrophic factors, antioxidants, calcium channel blockers, and gene therapy. Riluzole (riluzole) is one of the excitatory amino acid antagonists, is the first by the U.S. FDA and EU approval of the drug for the treatment of ALS. However, its efficacy is limited only prolong the patient's life a few months, and can not cure ALS. Further study of Traditional Chinese Medicine in China in particular is very important to research and development of new treatment of ALS drugs. Huperzine A (Huperzine A, HupA) is a novel Lycopodium alkaloids isolated from the the the folk medicine Melaleuca tower (Huperzia serrata) monomer, although it is a reversible high acetylcholinesterase inhibition agent, but on the pharmacological effects of Huperzine A in-depth studies have shown it against glutamate excitotoxicity, against oxidative stress, anti-apoptosis pathway cells to produce certain