Motor neuron diseases mutation

Wong, P. C., Pardo, C. A., Borchelt, D. R. et al. An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron 14 1105-1116,1995. 

Another motor neuron disease, which is rare and x-linked inheritance, shows certain similarities with ALS but has a much more benign course. It is so-called Kennedy s disease or x-linked spino-bulbar muscular atrophy (X-SBMA). It is caused by a mutation of the androgen receptor gene. A progressive spinal. 

Schmitt-John, T., Drepper, C., Mussmann, A., Hahn, P, Kuhlmann, M., Thiel, C., et al. (2005) Mutation of Vps54 causes motor neuron disease and defective spermiogene-sis in the wobbler mouse. Nat Genet 37, 1213-1215. 

The three-dimensional structure of NTE has not been experimentally determined, but a homology model of the patatin domain indicates that the active site serine (Ser ) is located on a nucleophilic elbow characteristic of serine hydrolases (Wijeyesakere et al., 2007). Moreover, the model indicates that the catalytic site of NTE consists of a novel Ser-Asp catalytic dyad, as in patatin and mammalian cytosolic phospholipase A2 (CPLA2), rather than the classical catalytic triad (Ser-Asp/Glu-His), as found in many serine hydrolases including AChE. Recently, mutations have been identified in NTE that are associated with motor neuron disease (Rainier et al., 2008). The mutations occur within the catalytic domain of NTE, but it is not yet known if they affect the catalytic function of the enzyme or alter some other property of the protein in order to produce disease. 

Wong PC, Pardo CA, Borchelt DR, Lee MK, Copeland NG, Jenkins NA, Sisodia SS, Cleveland DW, Price DL (1995) An Adverse property of a familial ALS-linked SODl mutation causes motor neuron disease characterized by vacuolar degeneradon of mitochondria. Neurorr Jurruary 14(6) 1105—1116. 

People with inherited motor neurone disease have mutations of SOD over 100 mutations have been identified. 

Hein, N.D., Stuckey J.A., Rainier, S.R., et al., 2010a. Constructs of human neuropathy target esterase catalytic domain containing mutations related to motor neuron disease have altered enzymatic properties. Toxicol. Lett. 1%, 67-73. 

Rainier, S., Bui, M., Mark, E., et al., 2008. Neuropathy target esterase gene mutations cause motor neuron disease. Am. J. Hum. Genet. 82, 780-785. 

Rainier, S., Albers, J.W, Dyck, P.J., et al., 2011. Motor neuron disease due to neuropathy target esterase gene mutation clinical features of the index families. Muscle Nerve 43 (19-25). 

The lack of zinc can also be a problem in biological systems and is responsible for disease states. For example, nitric oxide-dependent apoptosis can be induced in motor neurons by zinc-deficient SOD, and in some cases of amyotrophic lateral sclerosis, zinc-deficient SOD may participate in this type of oxidative mechanism involving nitric oxide.969 One form of hereditary human hair loss or alopecia was mapped to a specific gene and a mutation found in affected individuals. The gene encodes a single zinc finger transcription factor protein with restricted expression in the brain and skin.970 Zinc has been implicated in Alzheimer s via beta amyloid formation, and a role has been attributed for the cerebral zinc metabolism in the neuropathogenesis of Alzheimer s disease.971... 

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. 

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