Page - (000283) - in Biomedical Chemistry: Current Trends and Developments

20% of the cases, are mutations in a gene that encodes the copper/zinc- dependent superoxide dismutase protein (SOD1). In more recent studies, further mutations have been found by using genome wide association studies of patients afflicted with ALS, however, in many of these cases, the underlying molecular pathology is not yet known (Renton, 2014). Sporadic ALS does not have such target mutations, however, there are a few examples of environmental exposures that can result in ALS or ALS- like neurodegeneration and new gene targets with incomplete penetrance (Turner, 2013). One of the striking characteristics of familial ALS as well as SOD1 mutant mouse models is the high degree of selectivity that the disease shows for motor neurons over all other cells in the body, even though the mutant form of SOD1 protein is in many other cell types in the patient. A possible mechanism for this selectivity is based on excitatory neurotransmitter-mediated neuropathology, in particular glutamate. It is presently believed that motor neurons are especially susceptible to excitotoxicity because they are known to receive strong glutamatergic input. Additionally, spinal motor neurons have recently been found to express calcium-permeable AMPA receptors on their surface. Multiple lines of neurobiological research have resulted in the current understanding that calcium-permeable AMPA receptors play crucial roles in synaptic signaling and plasticity in the CNS. An overabundance of these receptors, coupled with glutamatergic excitation, could overwhelm the calcium buffering capacity of a cell, resulting in metabolic/mitochondrial breakdown followed by cell death. Presently, riluzole (Rilutek) is the only United States Food and Drug Administration approved therapeutic to treat ALS. The specific biological target of riluzole is controversial, but it is thought that the drug acts by reducing excitatory neurotransmission, resulting in the influx of less calcium into motor neurons slowing the progression of the disease. Unfortunately, riluzole is not a cure and only offers some of those suffering with ALS around 3 additional months of life. 3.2.6.2 Multiple Sclerosis (MS) MS is an inflammatory disease of the myelin sheath that insulates neurons in the brain and spinal cord. The breakdown of this insulator