Intermediate Filament Protein Inclusions

Abstract

This chapter provides an overview of the intermediate filaments (IF) and mallory body (MB) as a prototype of intermediate filament and discusses related inclusions such as neurofibrillary tangles (NFTs), Lewy bodies, Lewy body-like or skeinlike inclusions, Rosenthal fibers, inclusions in skeletal muscle fibers, and mallory bodies (MBs). Intermediate filament (IF) proteins are present in most of these inclusions, and in some types, such as MBs, they are the major constituent. Keratins are present in MBs in a different structural organization than in IF. The MB is one of the most common IF-related inclusions in diseases, and MB formation is a characteristic feature of liver cell injury in a variety of chronic liver diseases such as alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH). MBs are very stable structures and MB components are insoluble in high-salt buffers. MBs and other IF-related inclusions share several features, for example, all inclusions consist of misfolded IF proteins, ubiquitin, and, to a variable extent, other stress proteins. MBs are the characteristic features of a variety of liver diseases, but have to be distinguished from other cytoplasmic structures. On the basis of biochemical and ultrastructural analyses of human and murine MBs, the best criteria for making the distinction are the positivity for keratin and p62.