Sub Cellular Components
Just as different organs take responsibility for different task in the human body so different organelles take responsibility for different tasks in the cells which make up the body. Two organelles are of particular relevance in MND as they seem to be particularly affected by disease processes.
The mitochondrion is a sub-cellular component where the energy contained within food molecules is converted to a chemical energy that can be used in cells. Without mitochondria a cell is unable to obtain the energy it needs to survive.
Neurofilaments are used to strengthen and maintain the shape of neurones, where in some cases the length of the neurone can be a million times longer than the width of the cell. As a result of this great disparity between width and length neurones need additional strengthening to prevent breakage.
It was observed in 1966 that the mitochondria of damaged muscles in MND patients appeared not only to look abnormal but to be arranged abnormally along the muscle fibres. Subsequently abnormalities of mitochondria were noted in liver tissues, certain kinds of white blood cells and in particular the motor neurones of MND patients where they were found in association with depositions of broken neurofilaments. Further evidence indicated that mitochondria and neurofilaments are affected early in the disease process where mutated SOD1 is present and is probably responsible for this damage.
The most probable source for the generation of superoxide in the cell is the mitochondrion since that is where oxygen is caused to react with the carbon and hydrogen that comprise the major chemical components of fats and sugars. SOD1 is, therefore, found in abundance around the mitochondria.
It is possible that the loss of mitochondria from motor neurones sensitises them to further damage by excitotoxicity leading into the cascades mentioned earlier.
