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Lang A, Dassler E, Milenkovic I, et al. Variable expression of mitochondrial complex IV in the course of nigral intracellular accumulation of α-synuclein. Parkinsonism Relat Disord. 2021;90:57-61doi: 10.1016/j.parkreldis.2021.08.001.
Lang, A., Dassler, E., Milenkovic, I., Lutz, M. I., & Kovacs, G. G. (2021). Variable expression of mitochondrial complex IV in the course of nigral intracellular accumulation of α-synuclein. Parkinsonism & related disorders, 9057-61. https://doi.org/10.1016/j.parkreldis.2021.08.001
Lang, Alexandra, et al. "Variable expression of mitochondrial complex IV in the course of nigral intracellular accumulation of α-synuclein." Parkinsonism & related disorders vol. 90 (2021): 57-61. doi: https://doi.org/10.1016/j.parkreldis.2021.08.001
Lang A, Dassler E, Milenkovic I, Lutz MI, Kovacs GG. Variable expression of mitochondrial complex IV in the course of nigral intracellular accumulation of α-synuclein. Parkinsonism Relat Disord. 2021 Sep;90:57-61. doi: 10.1016/j.parkreldis.2021.08.001. Epub 2021 Aug 06. PMID: 34385008.
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Parkinsonism Relat Disord. 2021 Sep;90:57-61. doi: 10.1016/j.parkreldis.2021.08.001. Epub 2021 Aug 06.

Variable expression of mitochondrial complex IV in the course of nigral intracellular accumulation of α-synuclein.

Parkinsonism & related disorders

Alexandra Lang, Eva Dassler, Ivan Milenkovic, Mirjam I Lutz, Gabor G Kovacs

Affiliations

  1. Department of Neurosurgery, Medical University of Vienna, Vienna, Austria; Institute of Neurology, Medical University of Vienna, Vienna, Austria. Electronic address: [email protected].
  2. Institute of Neurology, Medical University of Vienna, Vienna, Austria; Medical University of Vienna, Department of Medicine II, Division of Angiology, Vienna, Austria. Electronic address: [email protected].
  3. Department of Neurology, Medical University of Vienna, Vienna, Austria. Electronic address: [email protected].
  4. Institute of Neurology, Medical University of Vienna, Vienna, Austria. Electronic address: [email protected].
  5. Institute of Neurology, Medical University of Vienna, Vienna, Austria; Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Laboratory Medicine Program & Krembil Brain Institute, University Health Network, Toronto, Ontario, Canada. Electronic address: [email protected].

PMID: 34385008 DOI: 10.1016/j.parkreldis.2021.08.001

Abstract

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disease characterized by the deposition of disease-associated α-synuclein, which is thought to follow a sequential distribution in the human brain. Accordingly, α-Synuclein pathology affects the substantia nigra (SN) only in Braak stage 3 out of 6. Moreover, intracellular accumulation of α-synuclein follows maturation from non-ubiquitinated (p62 negative) to ubiquitinated (p62 positive) forms (Lewy bodies). Mitochondrial dysfunction is thought to be a central player in the pathogenesis of PD. It is not clear whether the nigral neurons already show mitochondrial alterations in stages preceding the deposition of α-synuclein in the SN, and how deposition of pre-aggregates or ubiquitinated mature inclusions relate to this.

METHODS: Using cell-based morphometric immunohistochemistry we evaluated the volume density of mitochondrial complex-IV (COX-IV) immunoreactivity in SN neurons lacking or showing α-synuclein deposits in non-diseased individuals and those with Lewy body pathology Braak stage <3 lacking nigral α-synuclein pathology and Braak stage >3 with prominent nigral α-synuclein deposition.

RESULTS: Increased volume density of COX-IV immunoreactivity appears before detectable pathological α-synuclein in nigral neurons. The volume density decreases significantly as pathological pre-aggregates of α-synuclein accumulates in the neurons and remains at a low level in neurons with p62 positive Lewy bodies.

CONCLUSIONS: COX-IV expression shows a change before and during accumulation of α-synuclein in the SN underpinning the role of early mitochondrio protective therapy strategies in PD.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Keywords: COX-IV; Mitochondria; Oligomer; Parkinson's disease; p62; α-synuclein

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