Ubiquitin and the molecular pathology of neurodegenerative diseases.

Ubiquitin plays a central role in normal cellular function as well as in disease. It is possible to group ubiquitin-immunostained structures into several main groups, the most distinctive being the ubiquitin/intermediate filament/alphaB crystallin family of inclusions that seem to represent a general cellular response to abnormal proteins recently termed the aggresomal response. While ubiquitin immunohistochemistry is a very useful technique for detecting pathological changes and inclusion bodies in the nervous system this alone is not enough to classify inclusions, and a panel of antibodies is recommended to clarify any findings made by screening tissues with anti-ubiquitin. Several mechanistic possibilities now exist to explain the accumulation of ubiquitinated proteins in cells of the nervous system, understanding of which should lead to new therapeutic advances in the group of chronic neurodegenerative diseases.