PMID- 26456533
OWN - NLM
STAT- MEDLINE
DCOM- 20160727
LR  - 20191113
IS  - 2211-5374 (Electronic)
VI  - 4
IP  - 2
DP  - 2015
TI  - A MicroRNA-BDNF Negative Feedback Signaling Loop in Brain: Implications for 
      Alzheimer's Disease.
PG  - 101-8
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression 
      posttranscriptionally by interfering with translation of their target mRNAs. 
      Typically, miRNAs bind to the 3' UTRs of mRNAs to induce repression or 
      degradation. Neurotrophins are growth factors in brain required for neuronal 
      survival, synapse formation, and plasticity mechanisms. Neurotrophins are not 
      only regulated by miRNAs, but they in turn regulate miRNA expression. 
      Accumulating data indicate there is a regulatory negative feedback loop between 
      one ubiquitous neurotrophin, brain-derived neurotrophic factor (BDNF), and 
      miRNAs. That is, while BDNF treatment stimulates neuronal miRNA expression, 
      miRNAs generally function to inhibit expression of BDNF. This negative feedback 
      loop is maintained in a state of equilibrium in normal cells. However, in 
      Alzheimer's Disease (AD), a progressive neurodegenerative disorder resulting in 
      memory loss and eventually dementia that is characterized by reduced levels of 
      BDNF in brain, the balance between BDNF and miRNA is shifted toward inhibitory 
      control by miRNAs. Here, we will briefly review the evidence for a positive 
      action of BDNF on miRNA expression and a negative action of miRNAs on BDNF. We 
      propose that the reduction in BDNF that occurs in the AD brain is the result of 
      two independent mechanisms: 1) a failure in the proteolytic conversion of BDNF 
      precursor protein to its functional mature form, and 2) inhibition of BDNF gene 
      expression by miRNAs. The role of miRNAs in BDNF regulation should be considered 
      when developing BDNF-based therapeutic treatments for AD.
FAU - Keifer, Joyce
AU  - Keifer J
AD  - Neuroscience Group, Division of Basic Biomedical Sciences, University of South 
      Dakota Sanford School of Medicine, 414 E. Clark St., Vermillion, SD 57069, United 
      States. jkeifer@usd.edu.
FAU - Zheng, Zhaoqing
AU  - Zheng Z
FAU - Ambigapathy, Ganesh
AU  - Ambigapathy G
LA  - eng
GR  - R01 NS051187/NS/NINDS NIH HHS/United States
GR  - NS051187/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
PL  - United Arab Emirates
TA  - Microrna
JT  - MicroRNA (Shariqah, United Arab Emirates)
JID - 101631045
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Alzheimer Disease/*genetics/*metabolism
MH  - Animals
MH  - Brain/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*genetics/*metabolism/pharmacology
MH  - Down-Regulation
MH  - *Gene Expression Regulation/drug effects
MH  - Humans
MH  - MicroRNAs/*genetics
MH  - RNA Interference
MH  - *Signal Transduction/drug effects
EDAT- 2015/10/13 06:00
MHDA- 2016/07/28 06:00
CRDT- 2015/10/13 06:00
PHST- 2015/06/23 00:00 [received]
PHST- 2015/07/29 00:00 [revised]
PHST- 2015/08/07 00:00 [accepted]
PHST- 2015/10/13 06:00 [entrez]
PHST- 2015/10/13 06:00 [pubmed]
PHST- 2016/07/28 06:00 [medline]
AID - MIRNA-EPUB-69530 [pii]
AID - 10.2174/2211536604666150813152620 [doi]
PST - ppublish
SO  - Microrna. 2015;4(2):101-8. doi: 10.2174/2211536604666150813152620.