Mitochondrial function in Parkinson’s disease cybrids containing an nt2 neuron-like nuclear background

Esteves, A. Raquel; Domingues, Ana Filipa; Ferreira, Ildete L.; Januário, Cristina; Swerdlow, Russell H.; Oliveira, Catarina R.; Cardoso, Sandra M.

doi:10.1016/j.mito.2008.03.004

Cited by 102 publications

(95 citation statements)

References 42 publications

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“…45 On the other hand, Abeta and MPP + treatments in SH-SY5Y cells constitute a reliable model for screening potential neuroprotective compounds, since it mimics some aspects of neurodegeneration underlying the AD and PD, respectively. 46,47 Both stressors induce mitochondrial deficits, increase in ROS production, and apoptotic cell death 48,49 ; so all three compounds, due to their chemical properties, may act as strong antioxidants, and thus prevent ROS cellular damage.…”

Section: In Vitro Neuroprotective Activitymentioning

confidence: 99%

Bifunctional phenolic-choline conjugates as anti-oxidants and acetylcholinesterase inhibitors

Šebestı́k¹,

Marques²,

Falé

et al. 2010

Journal of Enzyme Inhibition and Medicinal Chemistry

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Section: In Vitro Neuroprotective Activitymentioning

confidence: 99%

Bifunctional phenolic-choline conjugates as anti-oxidants and acetylcholinesterase inhibitors

Šebestı́k¹,

Marques²,

Falé

et al. 2010

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…PD cybrid cell line ATP levels are reduced compared to those of control cybrids (31,33,34). The status of pathways influenced by cell bioenergetics is also altered.…”

Section: Pd Cybrid Modeling Of Other Pd-associated Pathologiesmentioning

confidence: 95%

“…PD cybrids appear to have ATP-dependent cytoskeletal changes, which manifest as microtubule depolymerization (31,33). a-synuclein protein is also altered in PD cybrids.…”

Section: Swerdlowmentioning

confidence: 99%

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Does Mitochondrial DNA Play a Role in Parkinson's Disease? A Review of Cybrid and Other Supportive Evidence

Swerdlow

2012

Antioxidants & Redox Signaling

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Significance: Mitochondria are currently believed to play an important role in the neurodysfunction and neurodegeneration that underlie Parkinson's disease (PD). Recent Advances: While it increasingly appears that mitochondrial dysfunction in PD can have different causes, it has been proposed that mitochondrial DNA (mtDNA) may account for or drive mitochondrial dysfunction in the majority of the cases. If correct, the responsible mtDNA signatures could represent acquired mutations, inherited mutations, or population-distributed polymorphisms. Critical Issues and Future Directions: This review discusses the case for mtDNA as a key mediator of PD, and especially focuses on data from studies of PD cytoplasmic hybrid (cybrid) cell lines. Antioxid. Redox Signal. 16, 950-964.

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“…Multiple groups have used the cybrid technique to show transfer of mitochondria and mtDNA from sporadic PD subject platelets produces cell lines with persistently reduced complex I activity (Swerdlow et al, 1996a;Gu et al, 1998;Esteves et al, 2008;Esteves et al, 2010). PD cybrid cell lines also have increased reactive oxygen species production, reduced mitochondrial calcium storage, less ATP production, depolarized mitochondria, and higher caspase 3 activity.…”

Section: Parkinson's Diseasementioning

confidence: 99%

Mitochondria in Neurodegeneration

Swerdlow

2011

Neural Metabolism in Vivo

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Many neurodegenerative diseases demonstrate abnormal mitochondrial morphology and biochemical dysfunction. Alterations are often systemic rather than brain-limited. Mitochondrial dysfunction may arise as a consequence of abnormal mitochondrial DNA, mutated nuclear proteins that interact directly or indirectly with mitochondria, or through unknown causes. In most cases it is unclear where mitochondria sit in relation to the overall disease cascades that ultimately causes neuronal dysfunction and death, and there is still controversy regarding the question of whether mitochondrial dysfunction is a necessary step in neurodegeneration. In this chapter we highlight and catalogue mitochondrial perturbations in some of the major neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). We consider data that suggest mitochondria may be critically involved in neurodegenerative disease neurodegeneration cascades. Keywordscybrid; mitochondria; mitochondrial DNA; neurodegenerative disease The quintessential neurodegenerative diseasesNeurodegenerative diseases are characterized by gradually progressive, selective loss of anatomically or physiologically related neuronal systems. The clinical syndromes associated with particular neuroanatomical patterns of cell dysfunction and loss are typically categorized by whether they initially affect cognition, movement, strength, coordination, sensation, vision, or autonomic control. Prototypical examples include AD, PD, ALS, and HD. HD is strictly an autosomal dominant disorder. With AD, PD, and ALS most cases are age-related and show sporadic epidemiology, although rare Mendelian variants do occur. As life expectancy continues to advance in developed countries the incidence of these disorders increases and will continue to do so.Mitochondrial dysfunction is a common theme in these diseases. Mitochondria are known to play a central role in many cell functions including ATP generation, intracellular Ca 2+ homeostasis, reactive oxygen species (ROS) formation, and apoptosis. Neurons are particularly dependent on mitochondria because of their high energy demands. It seems reasonable to hypothesize neurons are relatively intolerant of mitochondrial dysfunction. This assumption is supported by the fact that maternally inherited diseases with known homoplasmic or near-homoplasmic mitochondrial DNA (mtDNA) mutations tend to affect the central nervous system and muscle, the body's two most aerobic tissues.

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Mitochondrial function in Parkinson’s disease cybrids containing an nt2 neuron-like nuclear background

Cited by 102 publications

References 42 publications

Bifunctional phenolic-choline conjugates as anti-oxidants and acetylcholinesterase inhibitors

Bifunctional phenolic-choline conjugates as anti-oxidants and acetylcholinesterase inhibitors

Does Mitochondrial DNA Play a Role in Parkinson's Disease? A Review of Cybrid and Other Supportive Evidence

Mitochondria in Neurodegeneration

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