PATHOBIOCHEMICAL ASPECTS OF CYTOSKELETON COMPONENTS

This review summarizes pathobiochemical aspects of diseases, in which cytoskeletal components play a crucial role in pathogenesis. An attemp t to classify the disorders on the basis of phenotypic changes that oc cur in microfilaments, intermediate filaments and microtubuli was unsu ccessful. Three groups of disorders are presented: 1. cytoplasmic incl usions in specific diseases (merely descriptive); 2. diseases with gen etic defects in cytoskeletal proteins (a chain of causality from defec t to phenotype, in some cases with large gaps); 3. diseases with suspe cted involvement of cytoskeleton (hypothetical causal chain). Microfil aments are involved in certain pathogenetic processes on account of de fects in their associated proteins; in Duchenne muscular dystrophy, dy strophin is defective, while the defective protein in Rett syndrome is synapsin. Defects in spectrin and membrane anchor proteins lead to di sorders of the red cell membrane skeleton (congenital haemolytic anaem ias). Intermediate filaments accumulate in some types of cytoplasmic i nclusions, together with ubiquitin (Mallory bodies, desmin accumulatio n in some myopathies and others). A pathogenetic interpretation of thi s phenomenon is lacking. A genetic defect in certain types of keratin is the cause of epidermolysis bullosa. Interesting preliminary results are reviewed that reveal the crucial role of cytoskeletal components in a further group of diseases (intrahepatic cholestasis, Alzheimer di sease, pemphigus). These disorders are currently under investigation, or are of theoretical interest with respect to the cytoskeleton. Speci fic reactions of cytoskeletal components in serum, which might be used diagnostically, have not been found.