TY  - JOUR
A1  - Kim, Jae Ho
A1  - Franck, Julien
A1  - Kang, Taewook
A1  - Heinsen, Helmut
A1  - Ravid, Rivka
A1  - Ferrer, Isidro
A1  - Cheon, Mi Hee
A1  - Lee, Joo-Yong
A1  - Yoo, Jong Shin
A1  - Steinbusch, Harry W.
A1  - Salzet, Michel
A1  - Fournier, Isabelle
A1  - Park, Young Mok
T1  - Proteome-wide characterization of signalling interactions in the hippocampal CA4/DG subfield of patients with Alzheimer's disease
JF  - Scientific Reports
N2  - Alzheimer's disease (AD) is the most common form of dementia; however, mechanisms and biomarkers remain unclear. Here, we examined hippocampal CA4 and dentate gyrus subfields, which are less studied in the context of AD pathology, in post-mortem AD and control tissue to identify possible biomarkers. We performed mass spectrometry-based proteomic analysis combined with label-free quantification for identification of differentially expressed proteins. We identified 4,328 proteins, of which 113 showed more than 2-fold higher or lower expression in AD hippocampi than in control tissues. Five proteins were identified as putative AD biomarkers (MDH2, PCLO, TRRAP, YWHAZ, and MUC19 isoform 5) and were cross-validated by immunoblotting, selected reaction monitoring, and MALDI imaging. We also used a bioinformatics approach to examine upstream signalling interactions of the 113 regulated proteins. Five upstream signalling (IGF1, BDNF, ZAP70, MYC, and cyclosporin A) factors showed novel interactions in AD hippocampi. Taken together, these results demonstrate a novel platform that may provide new strategies for the early detection of AD and thus its diagnosis.
KW  - imaging mass spectrometry
KW  - neuron navigator 3
KW  - dentate gyrus
KW  - growth factor
KW  - mouse model
KW  - neurotrophic factor
KW  - entorhinal cortex
KW  - factor expression
KW  - oxidative stress
KW  - memory deficits
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151727
VL  - 5
IS  - 11138
ER  - 
TY  - JOUR
A1  - Ammar, Mohamed Raafet
A1  - Thahouly, Tamou
A1  - Hanauer, André
A1  - Stegner, David
A1  - Nieswandt, Bernhard
A1  - Vitale, Nicolas
T1  - PLD1 participates in BDNF-induced signalling in cortical neurons
JF  - Scientific Reports
N2  - The brain-derived neurotrophic factor BDNF plays a critical role in neuronal development and the induction of L-LTP at glutamatergic synapses in several brain regions. However, the cellular and molecular mechanisms underlying these BDNF effects have not been firmly established. Using in vitro cultures of cortical neurons from knockout mice for Pld1 and Rsk2, BDNF was observed to induce a rapid RSK2-dependent activation of PLD and to stimulate BDNF ERK1/2-CREB and mTor-S6K signalling pathways, but these effects were greatly reduced in Pld1\(^{-/-}\) neurons. Furthermore, phospho-CREB did not accumulate in the nucleus, whereas overexpression of PLD1 amplified the BDNF-dependent nuclear recruitment of phospho-ERK1/2 and phospho-CREB. This BDNF retrograde signalling was prevented in cells silenced for the scaffolding protein PEA15, a protein which complexes with PLD1, ERK1/2, and RSK2 after BDNF treatment. Finally PLD1, ERK1/2, and RSK2 partially colocalized on endosomal structures, suggesting that these proteins are part of the molecular module responsible for BDNF signalling in cortical neurons.
KW  - phospholipase D
KW  - ERK map kinease
KW  - long-term potentation
KW  - brain
KW  - protein RSK2
KW  - dendritic growth
KW  - neurite outgrowth
KW  - neurotrophic factor
KW  - coffin-lowry-syndrome
KW  - phosphatidic acid
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-139962
VL  - 5
IS  - 14778
ER  -