Neurofilaments and motor neuron disease

Nonapoptotic cell death caused by the inhibition of RNA polymerase disrupts organelle distribution

“…Furthermore, the calibers of these neurites were expanded locally at or near these sites. This dilatation of neurites is also evident when axonal flow is disturbed, a feature typically observed in patients with amyotrophic lateral sclerosis [21]. Thus, these findings support the idea that retrograde axonal transport was disrupted in the α-amanitin-treated neurons.…”

Hepatocyte Cytokeratins Are Hyperphosphorylated at Multiple Sites in Human Alcoholic Hepatitis and in a Mallory Body Mouse Model

“…However, a diversity of human diseases is associated with severe alterations of IFs. A common pathological feature of many IF-related diseases is the accumulation of intracytoplasmic inclusions consisting of modified IF proteins, for example in neurodegenerative diseases such as amyotrophic lateral sclerosis, Parkinson's disease, and Lewy body dementia [3][4][5][6] ; in neuromuscular disorders (eg, spheroid body myositis 7 ); and the formation of Mallory bodies (MBs) in alcoholic hepatitis (AH) and other liver disorders (eg, non-alcoholic steatohepatitis, Wilson's disease, primary biliary cirrhosis, Indian childhood cirrhosis, hepatocellular neoplasms 8 -11 ). Although the underlying pathogenetic mechanisms are as yet unclear, posttranslational modifications of IF proteins, such as phosphorylation, limited proteolysis, and crosslinking, may play a major role.…”

Protective effect of neurofilament heavy gene overexpression in motor neuron disease induced by mutant superoxide dismutase

“…This ubiquitous cytosolic enzyme is involved in the conversion of superoxide anion to hydrogen peroxide (3). Many lines of evidence suggest that SOD1 mutations cause ALS through mechanisms involving gain of deleterious activities (4)(5)(6). Several hypotheses have been proposed concerning the nature of the adverse activities of SOD1 mutants.…”

“…Previous studies with transgenic mice overexpressing normal or mutant neurofilament proteins (16)(17)(18)(19) and the discovery of very rare neurofilament heavy (NF-H) gene mutations in some ALS cases (6,20) have provided support for the idea that disorganization of neurofilaments can play a role in motor neuron disease. Of relevance to the present study was the report that overexpression of human NF-H in mice leads to a motor neuronopathy characterized by the formation of perikaryal neurofilamentous accumulations resembling those found in ALS and by the atrophy and slow degeneration of motor axons in old transgenic mice (16).…”