Asymmetric active site structures in yeast copper,zinc superoxide dismutase. 1. Reconstruction of apo-superoxide dismutase

Biochemistry ◽  
1984 ◽  
Vol 23 (19) ◽  
pp. 4324-4329 ◽  
Author(s):  
Joan C. Dunbar ◽  
Barton Holmquist ◽  
Jack T. Johansen
Keyword(s):  
Superoxide Dismutase ◽  
Active Site ◽  
Superoxide Dismutase 1 ◽  
Copper Zinc Superoxide Dismutase ◽  
Zinc Superoxide Dismutase ◽  
Copper Zinc

scholarly journals The neuroprotective effects of activated α7 nicotinic acetylcholine receptor against mutant copper–zinc superoxide dismutase 1-mediated toxicity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Taisei Ito ◽  
Masatoshi Inden ◽  
Tomoyuki Ueda ◽  
Yuta Asaka ◽  
Hisaka Kurita ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Motor Neurons ◽  
Superoxide Dismutase 1 ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Neuroprotective Effects ◽  
Nicotinic Acetylcholine ◽  
Copper Zinc Superoxide Dismutase ◽  
Zinc Superoxide Dismutase ◽  
Α7 Nachr ◽  
Copper Zinc

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective and progressive loss of motor neurons. Although many drugs have entered clinical trials, few have shown effectiveness in the treatment of ALS. Other studies have shown that the stimulation of α7 nicotinic acetylcholine receptor (nAChR) can have neuroprotective effects in some models of neurodegenerative disease, as well as prevent glutamate-induced motor neuronal death. However, the effect of α7 nAChR agonists on ALS-associated mutant copper–zinc superoxide dismutase 1 (SOD1) aggregates in motor neurons remains unclear. In the present study, we examined whether α7 nAChR activation had a neuroprotective effect against SOD1G85R-induced toxicity in a cellular model for ALS. We found that α7 nAChR activation by PNU282987, a selective agonist of α7 nAChR, exhibited significant neuroprotective effects against SOD1G85R-induced toxicity via the reduction of intracellular protein aggregates. This reduction also correlated with the activation of autophagy through the AMP-activated protein kinase (AMPK)–mammalian target of rapamycin (mTOR) signaling pathway. Furthermore, the activation of α7 nAChRs was found to increase the biogenesis of lysosomes by inducing translocation of the transcription factor EB (TFEB) into the nucleus. These results support the therapeutic potential of α7 nAChR activation in diseases that are characterized by SOD1G85R aggregates, such as ALS.

The Exploration of the Active-Site Cavity of Copper-Zinc Superoxide Dismutase

1988 ◽  
Vol 542 (1 Enzyme Engine) ◽  
pp. 37-52 ◽  
Author(s):  
IVANO BERTINI ◽  
LUCIA BANCI ◽  
CLAUDIO LUCHINAT ◽  
ROBERT A. HALLEWELL
Keyword(s):  
Superoxide Dismutase ◽  
Active Site ◽  
Copper Zinc Superoxide Dismutase ◽  
Zinc Superoxide Dismutase ◽  
Active Site Cavity ◽  
Copper Zinc

scholarly journals The neuroprotective effects of α7 nicotinic acetylcholine receptor against mutant copper-zinc superoxide dismutase 1-mediated toxicity

2020 ◽  
Author(s):  
Isao Hozumi ◽  
Taisei Ito ◽  
Masatoshi Inden ◽  
Tomoyuki Ueda ◽  
Yuta Asaka ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Motor Neurons ◽  
Superoxide Dismutase 1 ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Neuroprotective Effects ◽  
Nicotinic Acetylcholine ◽  
Copper Zinc Superoxide Dismutase ◽  
Zinc Superoxide Dismutase ◽  
Α7 Nachr ◽  
Copper Zinc

Abstract BackgroundAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective and progressive loss of motor neurons. Although many drugs have entered clinical trials, few have shown effectiveness in the treatment of ALS. Previous studies searching for causal genes associated with familial ALS identified the copper-zinc superoxide dismutase 1 (SOD1). Other studies have shown that the stimulation of α7 nicotinic acetylcholine receptor (nAChR) can have neuroprotective effects in some models of neurodegenerative disease, as well as prevent glutamate-induced motor neuronal death. However, the effect of α7 nAChR agonists on mutant SOD1 aggregates in motor neurons remains unclear.MethodsWe examined whether α7 nAChR activation had a neuroprotective effect against SOD1G85R-induced toxicity in a cellular model for ALS. Furthermore, the mechanism was also examined by Western blot analysis and qRT-PCR.ResultsWe found that α7 nAChR activation showed significant neuroprotective effects against SOD1G85R-induced toxicity via the reduction of intracellular protein aggregates. This reduction also correlated with the activation of autophagy through the AMP-activated protein kinase (AMPK)–mammalian target of rapamycin (mTOR) signaling pathway. Furthermore, the activation of α7 nAChRs was found to increase the biogenesis of lysosomes by inducing translocation of the transcription factor EB (TFEB) into the nucleus.ConclusionsThese results support the therapeutic potential of α7 nAChR activation in diseases that are characterized by SOD1G85R aggregates, such as ALS.

scholarly journals p-Coumaric Acid Has Protective Effects against Mutant Copper–Zinc Superoxide Dismutase 1 via the Activation of Autophagy in N2a Cells

2019 ◽  
Vol 20 (12) ◽  
pp. 2942 ◽  
Author(s):  
Tomoyuki Ueda ◽  
Taisei Ito ◽  
Hisaka Kurita ◽  
Masatoshi Inden ◽  
Isao Hozumi
Keyword(s):  
Superoxide Dismutase ◽  
Motor Neurons ◽  
Ethanol Extract ◽  
Protective Effects ◽  
Superoxide Dismutase 1 ◽  
Coumaric Acid ◽  
Neuroprotective Effects ◽  
Copper Zinc Superoxide Dismutase ◽  
Zinc Superoxide Dismutase ◽  
Copper Zinc

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective death of motor neurons. In previous our study, an ethanol extract of Brazilian green propolis (EBGP) prevented mutant copper–zinc superoxide dismutase 1 (SOD1mut)-induced neurotoxicity. This paper aims to reveal the effects of p-coumaric acid (p-CA), an active ingredient contained in EBGP, against SOD1mut-induced neurotoxicity. We found that p-CA reduced the accumulation of SOD1mut subcellular aggregation and prevented SOD1mut-associated neurotoxicity. Moreover, p-CA attenuated SOD1mut-induced oxidative stress and endoplasmic reticulum stress, which are significant features in ALS pathology. To examine the mechanism of neuroprotective effects, we focused on autophagy, and we found that p-CA induced autophagy. Additionally, the neuroprotective effects of p-CA were inhibited by chloroquine, an autophagy inhibiter. Therefore, these results obtained in this paper suggest that p-CA prevents SOD1mut-induced neurotoxicity through the activation of autophagy and provides a potential therapeutic approach for ALS.

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