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Int. J. Mol. Sci. 2017, 18(3), 545;

More Insight into BDNF against Neurodegeneration: Anti-Apoptosis, Anti-Oxidation, and Suppression of Autophagy

Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
Institute for Translation Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei 11221, Taiwan
Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei 11221, Taiwan
Department of Neurology, Taipei City Hospital, Taipei 11221, Taiwan
Author to whom correspondence should be addressed.
Academic Editor: Guiting Lin
Received: 31 January 2017 / Revised: 24 February 2017 / Accepted: 26 February 2017 / Published: 3 March 2017
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor)
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In addition to its well-established neurotrophic action, brain-derived neurotrophic factor (BDNF) also possesses other neuroprotective effects including anti-apoptosis, anti-oxidation, and suppression of autophagy. We have shown before that BDNF triggers multiple mechanisms to confer neuronal resistance against 3-nitropropionic acid (3-NP)-induced mitochondrial dysfunction in primary rat cortical cultures. The beneficial effects of BDNF involve the induction of anti-oxidative thioredoxin with the resultant expression of anti-apoptotic B-cell lymphoma 2 (Bcl-2) as well as erythropoietin (EPO)-dependent stimulation of sonic hedgehog (SHH). We further revealed that BDNF may bring the expression of sulfiredoxin, an ATP-dependent antioxidant enzyme, to offset mitochondrial inhibition in cortical neurons. Recently, we provided insights into another novel anti-oxidative mechanism of BDNF, which involves the augmentation of sestrin2 expression to endow neuronal resistance against oxidative stress induced by 3-NP; BDNF induction of sestrin2 entails the activation of a pathway involving nitric oxide (NO), cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG), and nuclear factor-κB (NF-κB). Apart from anti-apoptosis and anti-oxidation, we demonstrated in our most recent study that BDNF may activate the mammalian target of rapamycin (mTOR) with resultant activation of transcription factor c-Jun, thereby stimulating the expression of p62/sequestosome-1 to suppress heightened autophagy as a result of 3-NP exposure. Together, our results provide in-depth insight into multi-faceted protective mechanisms of BDNF against mitochondrial dysfunction commonly associated with the pathogenesis of many chronic neurodegenerative disorders. Delineation of the protective signaling pathways elicited by BDNF would endow a rationale to develop novel therapeutic regimens to halt or prevent the progression of neurodegeneration. View Full-Text
Keywords: 3-nitropropionic acid; p62; reactive oxygen species; sestrin2; sulfiredoxin 3-nitropropionic acid; p62; reactive oxygen species; sestrin2; sulfiredoxin

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Chen, S.-D.; Wu, C.-L.; Hwang, W.-C.; Yang, D.-I. More Insight into BDNF against Neurodegeneration: Anti-Apoptosis, Anti-Oxidation, and Suppression of Autophagy. Int. J. Mol. Sci. 2017, 18, 545.

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