Presence of Tissue Transglutaminase in Granular Endoplasmic Reticulum is Characteristic of Melanized Neurons in Parkinson's Disease Brain

Brain Pathology - Tập 21 Số 2 - Trang 130-139 - 2011
Micha M.M. Wilhelmus1, Robin Verhaar1, Gerda Andringa1, John G. J. M. Bol1, Patrick Cras2, Ling Shan3, Jeroen J.M. Hoozemans4, Benjamin Drukarch1
1Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, The Netherlands
2Department of Neurology, University Hospital of Antwerp, Edegem, Belgium
3Laboratory for Neuropsychiatric Disorders, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands.
4Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands

Tóm tắt

AbstractParkinson'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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Brain Pathology

Tập 21 Số 2

130-139

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