Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brain-derived neurotrophic factor (BDNF) is neuroprotective for motoneurons undergoing degeneration, including those in natural motor neuron disease (MND) in wobbler mice. To assess the role of BDNF in this model of MND, endogenous BDNF immunoreactivity was analyzed by semiquantitative video-image analysis. Affected cervical spinal cord motoneurons had significantly greater BDNF immunoreactivity compared to motoneurons of healthy littermates (P = 0.01) and affected lumbar spinal cord motoneurons (P = 0.008 at age 4 weeks; P = 0.005 at age 8 weeks). Neuronal nitric oxide synthase (n-NOS) immunocytochemistry revealed increased immunoreactivity in the affected cervical spinal cord motoneurons. Exogenous BDNF treatment partially inhibited the increased NOS activity, as quantitatively measured by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry. The mean number of NADPH-d(+) motoneurons in the cervical anterior horn decreased from 3.5 +/- 1.2 to 1.5 +/- 1.2 (P = 0.002). The increase in endogenous BDNF immunoreactivity in the affected spinal cord may be compensatory in diseased motoneurons, yet it appears to still be inadequate because exogenous BDNF treatment is required to suppress increased NOS activity in degenerating motoneurons. Our study indicates that BDNF is important in halting nitric oxide (NO)-mediated motor neuron degeneration, which has potential implications for the treatment of neurodegenerative disorders.
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PMID:Role of brain-derived neurotrophic factor in wobbler mouse motor neuron disease. 1126 18

Disturbances in Ca(2+) homeostasis and mitochondrial dysfunction have emerged as major pathogenic features in familial and sporadic forms of Amyotrophic Lateral Sclerosis (ALS), a fatal degenerative motor neuron disease. However, the distinct molecular ALS-pathology remains unclear. Recently, an activity-dependent Ca(2+) homeostasis deficit, selectively in highly vulnerable cholinergic motor neurons in the hypoglossal nucleus (hMNs) from a common ALS mouse model, the endstage superoxide dismutase SOD1(G93A) transgenic mouse, was described. This functional deficit was defined by a reduced hMN mitochondrial Ca(2+) uptake capacity and elevated Ca(2+) extrusion across the plasma membrane. To address the underlying molecular mechanisms, here we quantified mRNA-levels of respective potential mitochondrial and plasma membrane Ca(2+) transporters in individual, choline-acetyltransferase (ChAT) positive hMNs from wildtype (WT) and endstage SOD1(G93A) mice, by combining UV laser microdissection with RT-qPCR techniques, and specific data normalization. As ChAT cDNA levels as well as cDNA and genomic DNA levels of the mitochondrially encoded NADH dehydrogenase ND1 were not different between hMNs from WT and endstage SOD1(G93A) mice, these genes were used to normalize hMN-specific mRNA-levels of plasma membrane and mitochondrial Ca(2+) transporters, respectively. We detected about 2-fold higher levels of the mitochondrial Ca(2+) transporters MCU/MICU1, Letm1, and UCP2 in remaining hMNs from endstage SOD1(G93A) mice. These higher expression-levels of mitochondrial Ca(2+) transporters in individual hMNs were not associated with a respective increase in number of mitochondrial genomes, as evident from hMN specific ND1 DNA quantification. Normalized mRNA-levels for the plasma membrane Na(+)/Ca(2+) exchanger NCX1 were also about 2-fold higher in hMNs from SOD1(G93A) mice. Thus, pharmacological stimulation of Ca(2+) transporters in highly vulnerable hMNs might offer a neuroprotective strategy for ALS.
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PMID:Elevated mRNA-levels of distinct mitochondrial and plasma membrane Ca(2+) transporters in individual hypoglossal motor neurons of endstage SOD1 transgenic mice. 2545 14