Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.5.2 (NQO1)
 6,196 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

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive motor neuron disease for which only limited effective therapeutics are available. Currently, TAR DNA-binding protein 43 (TDP-43) is recognized as a pathological and biochemical marker for ALS. Increases in the levels of aggregated or mislocalized forms of TDP-43 might result in ALS pathology. Therefore, clearance pathways for intracellular protein aggregates have been suggested as potential therapeutic targets for the treatment of ALS. Here we report that treatment of motor neuron-like NSC34 cells overexpressing TDP-43 with diallyl trisulfide (DATS) induced neuronal autophagy and lysosomal clearance of TDP-43 and C-terminal TDP-43 fragments. We also observed that the antioxidant transcription factor NF-E2-related factor 2 (Nrf2) was accumulated in the nucleus and the expression of the antioxidant enzymes heme oxygenase1 (HO-1) and NAD(P)H:quinone oxidoreductase (NQO1) was increased. Consequently, DATS suppressed the increase in the levels of reactive oxygen species induced by TDP-43 expression. This study extends the findings of prior reports indicating that lower doses of DATS mediate cell survival in part by inducing autophagy and activating the Nrf2/antioxidant response element pathway.
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PMID:Diallyl Trisulfide Protects Motor Neurons from the Neurotoxic Protein TDP-43 via Activating Lysosomal Degradation and the Antioxidant Response. 3031 21