The cytoskeleton in neurodegenerative diseases

Abstract

In vitro and transgenic animal models are being used to demonstrate that different mutations impair protein function, promote tau fibrilization, or perturb tau gene splicing, leading to aberrant and distinct tau aggregates. For recognition of these disorders at neuropathological examination, immunohistochemistry is needed, and this may be combined with biochemistry and molecular genetics to properly determine the nosology of a particular case. As reviewed here, the identification of molecular genetic defects and biochemical alterations in cytoskeletal proteins of human neurodegenerative diseases has facilitated experimental studies and will promote the development of assays of molecules which inhibit abnormal neuronal IF and tau protein inclusions.

A mouse forward genetics screen identifies LISTERIN as an E3 ubiquitin ligase involved in neurodegeneration

“…2E Right). Abnormal phosphorylation of tau disrupts its affinity for microtubules and affects its contribution to maintaining axon integrity, which may provoke neurodegeneration (12). However, unlike the insoluble aggregates observed in AD patients, and in brains from certain AD mouse models (13), the hyperphosphorylated tau in lister mice remains soluble in sarkosyl buffer (Fig.…”

Spatial patterns of the tau pathology in progressive supranuclear palsy

“…PSP is therefore classified among the tauopathies, a group of disorders that also includes AD, Pick's disease (PiD), corticobasal degeneration (CBD), the NFT predominant form of senile dementia (NFT-SD), argyrophilic grain disease (AGD), and parkinsonism-dementia complex of Guam (Guam PDC) [15,16]. Abnormally enlarged neurons (EN) are present, especially in the inferior olivary nucleus [10] and throughout the neocortex [17].…”

Low concentration of GA activates a preconditioning response in HepG2 cells during oxidative stress—roles of Hsp90 and vimentin

“…IF mutations cause or predispose to more than 30 human diseases, including skin diseases, muscular dystrophies, premature aging, amyotrophic lateral sclerosis, and end-stage liver disease (Omary et al 2004). IF inclusions are characteristically seen in association with several liver, neuronal, or muscle disorders (Kurt et al 2004;Goldfarb et al 2004;Cairns et al 2004). Among the large protein family of IFs, vimentin is one of the most familiar members, as it is the major IF protein in mesenchymal cells.…”