PMID- 31456666
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 13
DP  - 2019
TI  - The Role of Altered BDNF/TrkB Signaling in Amyotrophic Lateral Sclerosis.
PG  - 368
LID - 10.3389/fncel.2019.00368 [doi]
LID - 368
AB  - Brain derived neurotrophic factor (BDNF) is well recognized for its 
      neuroprotective functions, via activation of its high affinity receptor, 
      tropomysin related kinase B (TrkB). In addition, BDNF/TrkB neuroprotective 
      functions can also be elicited indirectly via activation of adenosine 2A 
      receptors (A(2) (a) Rs), which in turn transactivates TrkB. Evidence suggests 
      that alterations in BDNF/TrkB, including TrkB transactivation by A(2) (a) Rs, can 
      occur in several neurodegenerative diseases, including amyotrophic lateral 
      sclerosis (ALS). Although enhancing BDNF has been a major goal for protection of 
      dying motor neurons (MNs), this has not been successful. Indeed, there is 
      emerging in vitro and in vivo evidence suggesting that an upregulation of 
      BDNF/TrkB can cause detrimental effects on MNs, making them more vulnerable to 
      pathophysiological insults. For example, in ALS, early synaptic 
      hyper-excitability of MNs is thought to enhance BDNF-mediated signaling, thereby 
      causing glutamate excitotoxicity, and ultimately MN death. Moreover, direct 
      inhibition of TrkB and A(2) (a) Rs has been shown to protect MNs from these 
      pathophysiological insults, suggesting that modulation of BDNF/TrkB and/or A(2) 
      (a) Rs receptors may be important in early disease pathogenesis in ALS. This 
      review highlights the relevance of pathophysiological actions of BDNF/TrkB under 
      certain circumstances, so that manipulation of BDNF/TrkB and A(2) (a) Rs may give 
      rise to alternate neuroprotective therapeutic strategies in the treatment of 
      neural diseases such as ALS.
FAU - Pradhan, Jonu
AU  - Pradhan J
AD  - Faculty of Medicine, School of Biomedical Sciences, The University of Queensland, 
      Brisbane, QLD, Australia.
FAU - Noakes, Peter G
AU  - Noakes PG
AD  - Faculty of Medicine, School of Biomedical Sciences, The University of Queensland, 
      Brisbane, QLD, Australia.
AD  - Queensland Brain Institute, The University of Queensland, Brisbane, QLD, 
      Australia.
FAU - Bellingham, Mark C
AU  - Bellingham MC
AD  - Faculty of Medicine, School of Biomedical Sciences, The University of Queensland, 
      Brisbane, QLD, Australia.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20190813
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC6700252
OTO - NOTNLM
OT  - A2aR
OT  - ALS
OT  - BDNF
OT  - MND
OT  - TrkB receptors
OT  - motor neurons
EDAT- 2019/08/29 06:00
MHDA- 2019/08/29 06:01
PMCR- 2019/01/01
CRDT- 2019/08/29 06:00
PHST- 2019/05/21 00:00 [received]
PHST- 2019/07/29 00:00 [accepted]
PHST- 2019/08/29 06:00 [entrez]
PHST- 2019/08/29 06:00 [pubmed]
PHST- 2019/08/29 06:01 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2019.00368 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2019 Aug 13;13:368. doi: 10.3389/fncel.2019.00368. 
      eCollection 2019.