PMID- 22009441
OWN - NLM
STAT- MEDLINE
DCOM- 20120119
LR  - 20211020
IS  - 1096-9896 (Electronic)
IS  - 0022-3417 (Print)
IS  - 0022-3417 (Linking)
VI  - 226
IP  - 1
DP  - 2012 Jan
TI  - Transglutaminase 1 and its regulator tazarotene-induced gene 3 localize to 
      neuronal tau inclusions in tauopathies.
PG  - 132-42
LID - 10.1002/path.2984 [doi]
AB  - Alzheimer's disease (AD), progressive supranuclear palsy (PSP), frontotemporal 
      dementia and parkinsonism linked to chromosome 17 (FTDP-17), and Pick's disease 
      (PiD) are commonly known as tauopathies. Neurodegeneration observed in these 
      diseases is linked to neuronal fibrillary hyperphosphorylated tau protein 
      inclusions. Transglutaminases (TGs) are inducible enzymes, capable of modifying 
      conformational and/or structural properties of proteins by inducing molecular 
      cross-links. Both transglutaminase 1 (TG1) and transglutaminase 2 (TG2) are 
      abundantly expressed in the brain and are associated with fibrillary 
      hyperphosphorylated tau protein inclusions in neurons of AD, so-called 
      neurofibrillary tangles (NFTs). However, other data obtained by our group 
      suggested that tau pathology in the brain may be primarily related to TG1 and not 
      to TG2 activity. To obtain more information on this issue, we set out to 
      investigate the association of TG1, TG2, and TG-catalysed cross-links with 
      fibrillary hyperphosphorylated tau inclusions in tauopathies other than AD, using 
      immunohistochemistry. We found strong TG1 and TG-catalysed cross-link staining in 
      neuronal tau inclusions characteristic of PSP, FTDP-17 with mutations in the tau 
      gene (FTDP-17T), and PiD brain, whereas, in contrast to AD, TG2 was only rarely 
      observed in these inclusions. Furthermore, using a biochemical approach, we 
      demonstrated that tau is a substrate for TG1-mediated cross-linking. 
      Interestingly, we found co-localization of the TG1 activator, tazarotene-induced 
      gene 3 (TIG3), in the neuronal tau inclusions of PSP, FTDP-17T, and PiD, but not 
      in NFTs of AD cases, indicating that these tau-containing protein aggregates are 
      not identical. We conclude that TG1-catalysed cross-linking, regulated by TIG3, 
      might play an important role in the formation of neuronal tau inclusions in PSP, 
      FTDP-17T, and PiD brain.
CI  - Copyright (c) 2011 Pathological Society of Great Britain and Ireland. Published by 
      John Wiley & Sons, Ltd.
FAU - Wilhelmus, Micha M M
AU  - Wilhelmus MM
AD  - Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU 
      University Medical Center, The Netherlands. m.wilhelmus@vumc.nl
FAU - de Jager, Mieke
AU  - de Jager M
FAU - Rozemuller, Annemieke J M
AU  - Rozemuller AJ
FAU - Breve, John
AU  - Breve J
FAU - Bol, John G J M
AU  - Bol JG
FAU - Eckert, Richard L
AU  - Eckert RL
FAU - Drukarch, Benjamin
AU  - Drukarch B
LA  - eng
GR  - R01 CA184027/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111018
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (PLAAT4 protein, human)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (tau Proteins)
RN  - EC 2.3.2.13 (Transglutaminases)
RN  - EC 2.3.2.13 (transglutaminase 1)
SB  - IM
MH  - Aged
MH  - Female
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - Immunohistochemistry
MH  - Inclusion Bodies/*metabolism/pathology
MH  - Male
MH  - Middle Aged
MH  - Neurons/*metabolism/pathology
MH  - Receptors, Retinoic Acid/*metabolism
MH  - Tauopathies/*metabolism/pathology
MH  - Transglutaminases/*metabolism
MH  - tau Proteins/*metabolism
PMC - PMC4756648
MID - NIHMS757764
EDAT- 2011/10/20 06:00
MHDA- 2012/01/20 06:00
PMCR- 2016/02/17
CRDT- 2011/10/20 06:00
PHST- 2011/05/17 00:00 [received]
PHST- 2011/07/05 00:00 [revised]
PHST- 2011/08/04 00:00 [accepted]
PHST- 2011/10/20 06:00 [entrez]
PHST- 2011/10/20 06:00 [pubmed]
PHST- 2012/01/20 06:00 [medline]
PHST- 2016/02/17 00:00 [pmc-release]
AID - 10.1002/path.2984 [doi]
PST - ppublish
SO  - J Pathol. 2012 Jan;226(1):132-42. doi: 10.1002/path.2984. Epub 2011 Oct 18.