“IF-pathies”: a broad spectrum of intermediate filament–associated diseases
M. Bishr Omary
M. Bishr Omary
Published July 1, 2009
Citation Information: J Clin Invest. 2009;119(7):1756-1762. https://doi.org/10.1172/JCI39894.
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Review Series

“IF-pathies”: a broad spectrum of intermediate filament–associated diseases

Abstract

Intermediate filaments (IFs) are encoded by the largest gene family among the three major cytoskeletal protein groups. Unique IF compliments are expressed in selective cell types, and this expression is reflected in their involvement, upon mutation, as a cause of or predisposition to more than 80 human tissue-specific diseases. This Review Series covers diseases and functional and structural aspects pertaining to IFs and highlights the molecular and functional consequences of IF-associated diseases (IF-pathies). Exciting challenges and opportunities face the IF field, including developing both a better understanding of the pathogenesis of IF-pathies and targeted therapeutic approaches.

Authors

M. Bishr Omary

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Figure 2

IFs and human disease.

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IFs and human disease. The involvement of IFs with human disease occurs ...
The involvement of IFs with human disease occurs at several levels. First, mutations in genes encoding IF proteins may either precipitate or predispose to a wide range of human diseases. It is also possible that natural selection has favored unique variants that may serve a protective role (16), although this hypothesis remains to be tested. Second, IF proteins, as a group, are essential for the formation of a variety of cell-specific inclusions that represent hallmarks of various diseases. Formation of these inclusions is generally independent of the presence of an IF mutation but does occur in the context of GFAP mutation in Alexander disease (18). Third, antibodies specific for IF proteins are routinely used in pathology laboratories across the world to help identify the origin of poorly differentiated tumors and are beginning to be used to assess tissue injury (directly in tissues, in blood, or in cerebrospinal fluid [CSF]) (16, 18). In addition, antibodies specific for IF proteins have been observed in the context of some autoimmune disease (16). ALS, amyotrophic lateral sclerosis; NIFID, neuronal IF inclusion disease.