The Origin of Amyotrophic Lateral Sclerosis

Each living cell requires energy in form of ATP for most of its processes. This energy is provided within a cell in a compartment that is termed mitochondrion. Within mitochondria, action of the mitochondrial respiratory chain generates the energy using electrons and oxygen. However and because the mitochondrial respiratory chain is so powerful, a side product of ATP is harmful ROS. During physical exercise energy demand increases, which is covered by a raised activity of the mitochondrial respiratory chain. But consequently, the risk of cellular damage inflicted by ROS also increases. To avoid damage done to cellular components, healthy individuals hold capable defense systems against ROS, notably enzymes of the GST, SOD and UCP classes. Of these, the UCP system is particularly noteworthy because of its capability to operate before ROS is generated. This UCP function is achieved by a reduction of the proton gradient across the inner mitochondrial membrane. However, because the proton gradient is coupled to ATP generation, a reduction of this gradient consequently diminishes energy production. This means that a cell has to deliberate whether ROS should be prevented at the cost of its cellular energy levels. But what happens if UCP activity is induced by external events or by exposure to specific substances that evoke a permanent energy deficit? In this book the physiological consequences of enhanced UCP activity are explained and as a result, can be connected to the origin of the neurodegenerative disease amyotrophic lateral sclerosis. Thus, potential treatment opportunities are provided that are missing so far. Further in this context, known risk factors for the initiation of ALS are discussed.