Next Article in Journal
Protective Effects of Ferulic Acid against Chronic Cerebral Hypoperfusion-Induced Swallowing Dysfunction in Rats
Next Article in Special Issue
Blood Biomarkers Predict the Cognitive Effects of Aripiprazole in Patients with Acute Schizophrenia
Previous Article in Journal
Cellular Reprogramming Using Protein and Cell-Penetrating Peptides
Previous Article in Special Issue
Low-Intensity Extracorporeal Shock Wave Therapy Enhances Brain-Derived Neurotrophic Factor Expression through PERK/ATF4 Signaling Pathway
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessReview
Int. J. Mol. Sci. 2017, 18(3), 545; doi:10.3390/ijms18030545

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

1
Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
2
Institute for Translation Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
3
College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
4
Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei 11221, Taiwan
5
Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei 11221, Taiwan
6
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)
View Full-Text   |   Download PDF [388 KB, uploaded 3 March 2017]   |  

Abstract

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
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top