Process In Amyotrophic Lateral Sclerosis Research Articles

Increased mitochondrial superoxide dismutase activity in Parkinson's disease but not amyotrophic lateral sclerosis motor cortex

Oxidative stress may contribute to the neurodegenerative process in amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). Motor cortex in PD is not affected and its inclusion in studies of free radical involvement in ALS pathogenesis could help elucidate whether oxidative stress is disease specific or a more widespread phenomenon present in the neurodegeneration. We have measured cytosolic and mitochondrial isoforms of superoxide dismutase (SOD), antioxidant enzymes involved in primary defence against free radical damage, in motor cortex of six patients with sporadic form of ALS (SALS), eight with PD and eight normal control subjects. We have found no difference in the activities of cytosolic and mitochondrial SOD between SALS and control motor cortex. Mitochondrial SOD activity in PD motor cortex was, however, significantly higher than in SALS and control motor cortex whereas activity of cytosolic SOD was lower than in two other groups although the differences were not statistically significant. Our findings indicate the presence of an altered antioxidant defence system in PD but not ALS upper motor neurons, suggesting that oxidative stress may be a widespread phenomenon in PD.

Selective vulnerability of alpha motor neurons in ALS: Relation to autoantibodies toward acetylcholinesterase (AChE) in ALS patients

The degenerative process in amyotrophic lateral sclerosis (ALS) concerns primarily alpha motor neurons in the spinal cord and brain stem, and neurons forming descending pathways to the cord, especially in the pyramidal tract. Some degeneration of large peripheral sensory nerve fibers often occurs too, but preganglionic autonomie neurons and gamma motor neurons are most often spared in the disease. The vulnerability of alpha motor neurons compared to other types of neurons in ALS is discussed in relation to retrograde axoplasmic transport from peripheral blood of foreign noxious macromolecules, interneuronal transport of such molecules, and neuronal surface structure properties relevant to uptake for retrograde axoplasmic transport. Certain differences in these aspects between alpha motor neurons and other neuronal types exist. Some differences concern the neuronal turnover of acetylcholinesterase (AChE), which could be of special interest in view of the recent demonstration of regular occurrence of autoantibodies towards this enzyme in ALS patients.

Distribution of calcium in central nervous system tissues and bones of rats maintained on calcium-deficient diets

Current changing epidemiological pattern in the Western Pacific area suggests a contribution of the environmental factors to the pathogenetic process of amyotrophic lateral sclerosis (ALS). The condition of unbalanced mineral levels found in the soil and drinking water samples from the ALS foci showing low content of calcium (Ca) and magnesium (Mg) plus high content of aluminum (Al) was experimentally mimicked in this study using rats. In the groups fed low Ca, low Ca-Mg, and low Ca-Mg plus high Al diets, serum Ca levels were lower than that in the group fed the standard diet. Ca content of CNS tissues showed higher values in the unbalanced diet groups, especially in the spinal cord of low Ca-Mg plus high Al diet group, than those in the standard diet group, determined by inductively-coupled plasma emission spectrometry (ICP). Ca content in heart, liver, kidney, and abdominal aorta in groups fed low Ca-Mg, and low Ca-Mg plus high Al diets was higher than that in low Ca, and standard group. Ca content in muscle in the three unbalanced diet groups was significantly higher than in the standard diet group. Ca and Mg contents in lumbar spine and cortical bone showed lower values in the unbalanced diet groups than those values in the standard diet group. These findings suggest that under the condition of derangement of bone mineralization induced by unbalanced mineral diets fed to the experimental rats, Ca and Mg may be mobilized from bone, keeping their content in soft tissues, including CNS tissue, for utilization of vital activities, thereby resulting in a deposition of Ca while maintaining an almost normal value of magnesium in the CNS tissues.