Neuro filament

Other diseases with disruptions in neurofilament organization include diabetic neuropathy and Charcot-Marie-Tooth disease. For these diseases, the disruption of neuro filaments may be a secondary effect as in the case of trembler axons or a direct effect. For example, some forms of Charcot-Marie-Tooth peripheral neuropathy result from mutations in a neurofilament subunit [22, 43]. In most cases, neuronal degeneration is an eventual consequence, but neuronal function may be impaired prior to substantial loss of neurons. Generally, disruptions of neurofilaments have the most severe consequences in large motor neurons, which is consistent with the fact that the largest neurons have the highest levels of neurofilament expression. 

In favorable systems, the coherent movement of neuro-filaments and microtubule proteins provides strong evidence for the structural hypothesis. Striking evidence was provided by pulse-labeling experiments in which NF proteins moved over periods of weeks as a bell-shaped wave with little or no trailing of NF protein. Similarly, coordinated transport of tubulin and MAPs makes sense only if MTs are being moved, since MAPs do not interact with unpolymerized tubulin [31]. 

The Ca +-dependent neutral proteases called calpains are found within the cells of higher animals. The 705-residue multidomain peptide chain of a chicken calpain contains a papain-like domain as well as a calmodulin-like domain. It presumably arose from fusion of the genes of these proteins. At least six calpains with similar properties are known. Some have a preference for myofibrillar proteins or neuro-filaments. They presumably function in normal turnover of these proteins and may play a role in numerous calcium-achvated cellular processes. 

Fig. 1. Whole-stage 22 chick embryo stained with a monoclonal antibody against neuro-filament, which detects axons within both the central and peripheral nervous systems.

On the one hand, the biochemical study of the neuro-pathological lesions led to the identification of their main molecular components. On the other hand, the study of rare, familial forms of Alzheimer s disease, frontotemporal dementia and Parkinson s disease led to the identification of gene defects that cause inherited variants of the different diseases. Remarkably, in these cases, the defective genes have been found to encode or increase the expression of the main components of the neuropathological lesions. It has therefore been established that the basis of the familial forms of these diseases is a toxic property conferred by mutations in the proteins that make up the filamentous lesions. A corollary of this insight is that a similar toxic property may also underlie the much more common, sporadic forms of the diseases. 

Also prevalent in ALS are reactive astrocytes, which stain intensively for the intermediate filament, glial fibrillary acidic protein (GFAP). These reactive astrocytes, with a hypertrophied appearance, are present throughout areas of degeneration. Reactive astrocytes can have multiple roles including a neuro-protective function (Liberto et al., 2004). 

Hoefler H, Denk H, Lackinger E, et al. Immunocytochemical demonstration of intermediate filament cytoskeleton proteins in 78. human endocrine tissues and (neuro-) endocrine tumors. Virch... 

The connecting site between the motor neuron and the muscle is called the neuromuscular junction. One motor neuron can have branches to many muscle libers, and these together are called a motor unit. When the nerve impulse reaches the end of the nerve fiber, a neuro-transmitter called acetylcholine is released into the motor end plate of the muscle. This in turn causes the release of Ca ions deep into the muscle fiber. The presence of Ca ions causes cross-bridges to be formed between actin and myosin filaments in the sarcomeres. The actin filaments slide inward along the myosin filaments, causing the muscle fiber to contract. 

---