Session Information
Date: Tuesday, June 21, 2016
Session Title: Parkinson's disease: Pathophysiology
Session Time: 12:30pm-2:00pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To investigate the expression of mitochondrial COX-IV during the progression of Parkinson’s disease.
Background: Parkinson’s disease (PD) is a neurodegenerative disease characterized by the deposition of disease-associated α-synuclein, which appears in the brain following a hierarchical manner. α-Synuclein pathology affects substantial nigra only in stage 3 out of 6, and earlier stages represent non-motor phases. Moreover, intracellular accumulation of α-synuclein follows a 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 cytopathological alterations preceding the deposition of α-synuclein and whether mitochondrial alterations of nigral neurons differ when so called pre-aggregates or ubiquitinated mature inclusions are present in the cell.
Methods: Using cell-based morphometric immunohistochemistry we evaluated the volume density of mitochondrial cytochrome c oxidase (complex IV of the electron transport chain, COX-IV) immunoreacivity in neurons in the substatia nigra (SN) lacking or showing α-synuclein deposits in individuals without and with PD. In PD cases we examined samples from cases with Braak stage 2 lacking SN α-synuclein pathology and Braak stage 6 with prominent SN α-synuclein deposition.
Results: Increased volume density of mitochondrial COX-IV immunoreacitvity appears before pathological α-synuclein is detected in nigral neurons. The volume density decreases significantly as pathological pre-aggregates of α-synuclein accumulates in the neurons and further remains in neurons with p62 positive Lewy bodies.
Conclusions: COX-IV expression shows a dynamic change before and during accumulation of α-synuclein in the substantia nigra underpinning the role of early mitochondrioprotective therapeutical strategies in PD.
Annual meeting of Austrian Parkinson Society.
To cite this abstract in AMA style:
I. Milenkovic, E. Dassler, M. Weber, G.G. Kovacs. Mitochondrial response precedes intracellular accumulation of α-synuclein in Parkinson’s disease [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/mitochondrial-response-precedes-intracellular-accumulation-of-synuclein-in-parkinsons-disease/. Accessed December 10, 2024.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/mitochondrial-response-precedes-intracellular-accumulation-of-synuclein-in-parkinsons-disease/