Title
Presence of tissue transglutaminase in granular endoplasmic reticulum is characteristic of melanized neurons in Parkinson's disease brain Presence of tissue transglutaminase in granular endoplasmic reticulum is characteristic of melanized neurons in Parkinson's disease brain
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Pittsburgh, Pa ,
Subject
Human medicine
Source (journal)
Brain pathology / International Society of Neuropathology. - Pittsburgh, Pa
Volume/pages
21(2011) :2 , p. 130-139
ISSN
1015-6305
ISI
000286626400002
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Parkinson's disease (PD) is characterized by the accumulation of α-synuclein aggregates and degeneration of melanized neurons. The tissue transglutaminase (tTG) enzyme catalyzes molecular protein cross-linking. In PD brain, tTG-induced cross-links have been identified in α-synuclein monomers, oligomers and α-synuclein aggregates. However, whether tTG and α-synuclein occur together in PD affected neurons remains to be established. Interestingly, using immunohistochemistry, we observed a granular distribution pattern of tTG, characteristic of melanized neurons in PD brain. Apart from tTG, these granules were also positive for typical endoplasmic reticulum (ER)-resident chaperones, that is, protein disulphide isomerase, ERp57 and calreticulin, suggesting a direct link to the ER. Additionally, we observed the presence of phosphorylated pancreatic ER kinase (pPERK), a classical ER stress marker, in tTG granule positive neurons in PD brain, although no subcellular colocalization of tTG and pPERK was found. Our data therefore suggest that tTG localization to granular ER compartments is specific for stressed melanized neurons in PD brain. Moreover, as also α-synuclein aggregates were observed in tTG granule positive neurons, these results provide a clue to the cellular site of interaction between α-synuclein and tTG.
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