title: Lewy Bodies and the Mechanisms of Neuronal Cell Death in Parkinson's Disease and Dementia with Lewy Bodies.
abstract: Neuronal loss in specific brain regions and neurons with intracellular inclusions termed Lewy bodies are the pathologic hallmark in both Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Lewy bodies comprise of aggregated intracellular vesicles and proteins and α-synuclein is reported to be a major protein component. Using human brain tissue from control, PD and DLB and light and confocal immunohistochemistry with antibodies to superoxide dismutase 2 as a marker for mitochondria, α-synuclein for Lewy bodies and βIII Tubulin for microtubules we have examined the relationship between Lewy bodies and mitochondrial loss. We have shown microtubule regression and mitochondrial and nuclear degradation in neurons with developing Lewy bodies. In PD, multiple Lewy bodies were often observed with α-synuclein interacting with DNA to cause marked nuclear degradation. In DLB, the mitochondria are drawn into the Lewy body and the mitochondrial integrity is lost. This work suggests that Lewy bodies are cytotoxic. In DLB, we suggest that microtubule regression and mitochondrial loss results in decreased cellular energy and axonal transport that leads to cell death. In PD, α-synuclein aggregations are associated with intact mitochondria but interacts with and causes nuclear degradation which may be the major cause of cell death.
authors.affiliation: Department of Human Physiology, Flinders Medical Science and Technology, School of Medicine, Flinders University, South Australia.
authors.forename: John H T
authors.initials: JH
authors.lastname: Power
authors.affiliation: Department of Human Physiology, Flinders Medical Science and Technology, School of Medicine, Flinders University, South Australia.
authors.forename: Olivia L
authors.initials: OL
authors.lastname: Barnes
authors.affiliation: Department of Human Physiology, Flinders Medical Science and Technology, School of Medicine, Flinders University, South Australia.
authors.forename: Fariba
authors.initials: F
authors.lastname: Chegini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D016923:Cell Death; D002467:Cell Nucleus / Q000648:ultrastructure; D003576:Electron Transport Complex IV / Q000032:analysis; D005260:Female; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology*; D020961:Lewy Body Disease / Q000473:pathology*; D008297:Male; D008870:Microtubules / Q000648:ultrastructure; D008875:Middle Aged; D008928:Mitochondria / Q000648:ultrastructure; D009410:Nerve Degeneration / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010300:Parkinson Disease / Q000473:pathology*; D013482:Superoxide Dismutase / Q000032:analysis; D051844:alpha-Synuclein / Q000032:analysis; D000099156:Superoxide Dismutase 2
chemical_list: D015415:Biomarkers; D003576:Electron Transport Complex IV; D009419:Nerve Tissue Proteins; D013482:Superoxide Dismutase; D051844:alpha-Synuclein; D000099156:Superoxide Dismutase 2; C117108:cytochrome C oxidase subunit II
keywords: alpha synuclein; confocal microscopy; immunohistochemistry; microtubules; mitochondria; neurodegeneration