PMID- 27878758
OWN - NLM
STAT- MEDLINE
DCOM- 20180727
LR  - 20181113
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Print)
IS  - 0893-7648 (Linking)
VI  - 54
IP  - 10
DP  - 2017 Dec
TI  - Gender-Specific Expression of Ubiquitin-Specific Peptidase 9 Modulates Tau 
      Expression and Phosphorylation: Possible Implications for Tauopathies.
PG  - 7979-7993
LID - 10.1007/s12035-016-0299-z [doi]
AB  - Public transcriptomic studies have shown that several genes display pronounced 
      gender differences in their expression in the human brain, which may influence 
      the manifestations and risk for neuronal disorders. Here, we apply a 
      transcriptome-wide analysis to discover genes with gender-specific expression and 
      significant alterations in public postmortem brain tissue from Alzheimer's 
      disease (AD) patients compared to controls. We identify the sex-linked 
      ubiquitin-specific peptidase 9 (USP9) as an outstanding candidate gene with 
      highly significant expression differences between the genders and male-specific 
      underexpression in AD. Since previous studies have shown that USP9 can modulate 
      the phosphorylation of the AD-associated protein MAPT, we investigate functional 
      associations between USP9 and MAPT in further detail. After observing a high 
      positive correlation between the expression of USP9 and MAPT in the public 
      transcriptomics data, we show that USP9 knockdown results in significantly 
      decreased MAPT expression in a DU145 cell culture model and a 
      concentration-dependent decrease for the MAPT orthologs mapta and maptb in a 
      zebrafish model. From the analysis of microarray and qRT-PCR experiments for the 
      knockdown in DU145 cells and prior knowledge from the literature, we derive a 
      data-congruent model for a USP9-dependent regulatory mechanism modulating MAPT 
      expression via BACH1 and SMAD4. Overall, the analyses suggest USP9 may contribute 
      to molecular gender differences observed in tauopathies and provide a new target 
      for intervention strategies to modulate MAPT expression.
FAU - Koglsberger, Sandra
AU  - Koglsberger S
AD  - Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7 
      avenue des Hauts Fourneaux, 4362, Esch-sur-Alzette, Luxembourg.
FAU - Cordero-Maldonado, Maria Lorena
AU  - Cordero-Maldonado ML
AD  - Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7 
      avenue des Hauts Fourneaux, 4362, Esch-sur-Alzette, Luxembourg.
FAU - Antony, Paul
AU  - Antony P
AD  - Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7 
      avenue des Hauts Fourneaux, 4362, Esch-sur-Alzette, Luxembourg.
FAU - Forster, Julia Ilona
AU  - Forster JI
AD  - Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7 
      avenue des Hauts Fourneaux, 4362, Esch-sur-Alzette, Luxembourg.
FAU - Garcia, Pierre
AU  - Garcia P
AD  - Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7 
      avenue des Hauts Fourneaux, 4362, Esch-sur-Alzette, Luxembourg.
FAU - Buttini, Manuel
AU  - Buttini M
AD  - Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7 
      avenue des Hauts Fourneaux, 4362, Esch-sur-Alzette, Luxembourg.
FAU - Crawford, Alexander
AU  - Crawford A
AD  - Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7 
      avenue des Hauts Fourneaux, 4362, Esch-sur-Alzette, Luxembourg.
FAU - Glaab, Enrico
AU  - Glaab E
AUID- ORCID: 0000-0003-3977-7469
AD  - Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7 
      avenue des Hauts Fourneaux, 4362, Esch-sur-Alzette, Luxembourg. 
      enrico.glaab@uni.lu.
LA  - eng
GR  - C2014002/BrightFocus Foundation (US)/
GR  - I1R-DIR-PAU-15ABAD/Fondation Wivine/
PT  - Journal Article
DEP - 20161123
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (tau Proteins)
RN  - EC 3.4.19.12 (Ubiquitin-Specific Proteases)
SB  - IM
MH  - Alzheimer Disease/*metabolism
MH  - Animals
MH  - Brain/metabolism
MH  - Female
MH  - Gene Expression Regulation, Developmental/*physiology
MH  - Humans
MH  - Male
MH  - Phosphorylation
MH  - Tauopathies/*metabolism
MH  - Ubiquitin-Specific Proteases/*metabolism
MH  - Zebrafish
MH  - tau Proteins/*metabolism
PMC - PMC5684262
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Gender differences
OT  - Tau
OT  - Tauopathies
OT  - Transcriptomics
OT  - Zebrafish
COIS- The authors declare that they have no conflict of interest.
EDAT- 2016/11/24 06:00
MHDA- 2018/07/28 06:00
PMCR- 2016/11/23
CRDT- 2016/11/24 06:00
PHST- 2016/05/22 00:00 [received]
PHST- 2016/11/14 00:00 [accepted]
PHST- 2016/11/24 06:00 [pubmed]
PHST- 2018/07/28 06:00 [medline]
PHST- 2016/11/24 06:00 [entrez]
PHST- 2016/11/23 00:00 [pmc-release]
AID - 10.1007/s12035-016-0299-z [pii]
AID - 299 [pii]
AID - 10.1007/s12035-016-0299-z [doi]
PST - ppublish
SO  - Mol Neurobiol. 2017 Dec;54(10):7979-7993. doi: 10.1007/s12035-016-0299-z. Epub 
      2016 Nov 23.