Cells, including those of the nervous system, respond to damage by an increase in the synthesis of a family of
proteins called '
stress proteins' which are amongst the most conserved gene products in evolution suggesting fundamental roles in cell metabolism. Stress-induced
proteins have functions in normal cells, particularly for the importation of
protein into membrane-limited organelles, and their up-regulation following stress is thought to be cytoprotective, by protecting
proteins and organelles from damage.
Ubiquitin is an important
protein induced by cell stress. It is only found in nucleated cells and has several known functions; the most investigated being as a co-factor for the non-lysosomal intracellular degradation of abnormal or short lived
proteins. Morphological studies using immunohistochemistry to localize
ubiquitin protein conjugates have revealed that
ubiquitin is a component of many of the filamentous inclusion bodies characteristic of
neurodegenerative diseases, suggesting activation of a common neuronal response in this type of disease process. Immunohistochemical localization of
ubiquitin conjugates has provided a new tool for the sensitive detection of such inclusions and has resulted in the identification of novel inclusion bodies in all cases of
motor neuron disease. Preliminary work on
enzymes involved in
ubiquitin metabolism suggest that there are several possible mechanisms for the formation of inclusion bodies and may provide indirect evidence for the dynamics of inclusion body formation. Work in other areas of pathology indicate important roles for the
stress proteins in immune surveillance and autoimmunity and it is likely that the general principles which are currently evolving will also have an impact in neuropathology.