PMID- 20007471
OWN - NLM
STAT- MEDLINE
DCOM- 20100119
LR  - 20220408
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 29
IP  - 49
DP  - 2009 Dec 9
TI  - Brain-derived neurotrophic factor reduces amyloidogenic processing through 
      control of SORLA gene expression.
PG  - 15472-8
LID - 10.1523/JNEUROSCI.3960-09.2009 [doi]
AB  - Sorting protein-related receptor with A-type repeats (SORLA) is a major risk 
      factor in cellular processes leading to Alzheimer's disease (AD). It acts as 
      sorting receptor for the amyloid precursor protein (APP) that regulates 
      intracellular trafficking and processing into amyloidogenic-beta peptides (A 
      beta). Overexpression of SORLA in neurons reduces while inactivation of gene 
      expression (as in knock-out mouse models) accelerates amyloidogenic processing 
      and senile plaque formation. The current study aimed at identifying molecular 
      pathways that control SORLA gene transcription in vivo and that may contribute to 
      low levels of receptor expression in the brain of patients with AD. Using 
      screening approaches in primary neurons, we identified brain-derived neurotrophic 
      factor (BDNF) as a major inducer of Sorla that activates receptor gene 
      transcription through the ERK (extracellular regulated kinase) pathway. In line 
      with a physiological role as regulator of Sorla, expression of the receptor is 
      significantly impaired in mouse models with genetic (Bdnf(-/-)) or 
      disease-related loss of BDNF activity in the brain (Huntington's disease). 
      Intriguingly, exogenous application of BDNF reduced A beta production in primary 
      neurons and in the brain of wild-type mice in vivo, but not in animals 
      genetically deficient for Sorla. These findings demonstrate that the beneficial 
      effects ascribed to BDNF in APP metabolism act through induction of Sorla that 
      encodes a negative regulator of neuronal APP processing.
FAU - Rohe, Michael
AU  - Rohe M
AD  - Max Delbrueck Center for Molecular Medicine, Charite-Universitatsmedizin Berlin, 
      D-13125 Berlin, Germany.
FAU - Synowitz, Michael
AU  - Synowitz M
FAU - Glass, Rainer
AU  - Glass R
FAU - Paul, Steven M
AU  - Paul SM
FAU - Nykjaer, Anders
AU  - Nykjaer A
FAU - Willnow, Thomas E
AU  - Willnow TE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, LDL)
RN  - 0 (Sorl1 protein, mouse)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
SB  - IM
MH  - Amyloid Precursor Protein Secretases/metabolism
MH  - Amyloid beta-Peptides/*metabolism
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Animals
MH  - Animals, Newborn
MH  - Brain/enzymology/*metabolism
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Cells, Cultured
MH  - Cerebral Cortex/enzymology/metabolism
MH  - Disease Models, Animal
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Gene Expression Regulation
MH  - Humans
MH  - Huntington Disease/enzymology/metabolism
MH  - MAP Kinase Signaling System
MH  - Membrane Transport Proteins/genetics/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Neurons/enzymology/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptor, trkB/metabolism
MH  - Receptors, LDL/genetics/*metabolism
PMC - PMC6666105
EDAT- 2009/12/17 06:00
MHDA- 2010/01/20 06:00
PMCR- 2010/06/09
CRDT- 2009/12/17 06:00
PHST- 2009/12/17 06:00 [entrez]
PHST- 2009/12/17 06:00 [pubmed]
PHST- 2010/01/20 06:00 [medline]
PHST- 2010/06/09 00:00 [pmc-release]
AID - 29/49/15472 [pii]
AID - 3553140 [pii]
AID - 10.1523/JNEUROSCI.3960-09.2009 [doi]
PST - ppublish
SO  - J Neurosci. 2009 Dec 9;29(49):15472-8. doi: 10.1523/JNEUROSCI.3960-09.2009.