Detection of Respiratory Chain Defects in Cultivated Skin Fibroblasts and Skeletal Muscle of Patients with Parkinson's Disease

Wiedemann, Falk R.; Winkler, Kirstin; Lins, Hartmut; Wallesch, Claus‐W.; Kunz, Wolfram S.

doi:10.1111/j.1749-6632.1999.tb07870.x

Cited by 26 publications

(28 citation statements)

References 10 publications

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“…In a preliminary study, we have applied inhibitor titrations of oxygen consumption of saponin-permeabilized muscle fibers and digitonin-permeabilized skin fibroblasts to determine the flux control of complexes I and IV in samples from 13 PD patients [30]. In the work presented here, we extended this study and determined the metabolic effects of the complex I deficiency in fibroblasts.…”

Section: Introductionmentioning

confidence: 91%

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Effect of coenzyme Q10 on the mitochondrial function of skin fibroblasts from Parkinson patients

Winkler-Stuck

Wiedemann

Wallesch

et al. 2004

Journal of the Neurological Sciences

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Section: Introductionmentioning

confidence: 91%

“…The study was approved by the ethics committee of the Medical Faculty, Magdeburg University. Selected data from patients 1 to 13 were presented in abstract form [30].…”

Section: Patientsmentioning

confidence: 99%

Effect of coenzyme Q10 on the mitochondrial function of skin fibroblasts from Parkinson patients

Winkler-Stuck

Wiedemann

Wallesch

et al. 2004

Journal of the Neurological Sciences

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“…Indeed, mitochondrial and bioenergetic dysfuntions, which are key pathological processes in Parkinson's disease, were shown first in fibroblasts from patients. [33][34][35] We used fibroblasts from control individuals and patients with early psychosis (EP) to avoid confounding effects of long-term medication and illness. Moreover, analyses were stratified based on the patients' genotype in GCLC GAG tri-nucleotide repeats to better determine the anomalies associated with an altered redox control.…”

Section: Introductionmentioning

confidence: 99%

Impaired Metabolic Reactivity to Oxidative Stress in Early Psychosis Patients

Fournier¹,

Ferrari

Baumann

et al. 2014

Schizophrenia Bulletin

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Because increasing evidence point to the convergence of environmental and genetic risk factors to drive redox dysregulation in schizophrenia, we aim to clarify whether the metabolic anomalies associated with early psychosis reflect an adaptation to oxidative stress. Metabolomic profiling was performed to characterize the response to oxidative stress in fibroblasts from control individuals (n = 20) and early psychosis patients (n = 30), and in all, 282 metabolites were identified. In addition to the expected redox/ antioxidant response, oxidative stress induced a decrease of lysolipid levels in fibroblasts from healthy controls that were largely muted in fibroblasts from patients. Most notably, fibroblasts from patients showed disrupted extracellular matrix-and arginine-related metabolism after oxidative stress, indicating impairments beyond the redox system. Plasma membrane and extracellular matrix, 2 regulators of neuronal activity and plasticity, appeared as particularly susceptible to oxidative stress and thus provide novel mechanistic insights for pathophysiological understanding of early stages of psychosis. Statistically, antipsychotic medication at the time of biopsy was not accounting for these anomalies in the metabolism of patients' fibroblasts, indicating that they might be intrinsic to the disease. Although these results are preliminary and should be confirmed in a larger group of patients, they nevertheless indicate that the metabolic signature of reactivity to oxidative stress may provide reliable early markers of psychosis. Developing protective measures aimed at normalizing the disrupted pathways should prevent the pathological consequences of environmental stressors.

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“…This observation has led to the theory that the mitochondrial dysfunction caused by oxidative stress plays a central role in ageing 30,31 . With PD arising at old age and with mitochondrial function specifically known to be compromised in a variety of cell types in PD patients 32,33,34,35 , the mitochondrial theory of aging broadly views PD as yet another manifestation of this phenomenon 14 . It is conceivable that accumulated random damage, possibly in mitochondrial DNA and due to oxidative stress, eventually triggers the gene expression program of a cell to shift to the PD-state.…”

Section: The Role Of Ageing In Pdmentioning

confidence: 99%

The universal non-neuronal nature of Parkinson's disease: A theory

Valente

Adilbayeva

Tokay

et al. 2016

Preprint

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Parkinson's disease (PD) is one of the most common neurodegenerative disorders, yet the etiology of the majority of its cases remains unknown. In this article, relevant published evidence is interpreted and integrated into a comprehensive hypothesis on the nature, origin and intercellular mode of propagation of sporadic PD. We propose to characterize sporadic PD as a pathological deviation in the global gene expression program of a cell: the PD expression-state, or PD-state for short. A universal cell-generic state, the PD-state deviation would be particularly damaging in a neuronal context, ultimately leading to neuron death and the ensuing observed clinical signs. We review why ageing associated accumulated damage caused by oxidative stress in mitochondria could be the trigger for a primordial cell to shift to the PD-state. We propose that hematopoietic cells could be the first to acquire the PD-state, at hematopoiesis, from the disruption in reactive oxygen species (ROS) homeostasis that arises with age in the hematopoietic stem-cell niche. We argue that cellular ageing is nevertheless unlikely to explain the shift to the PD-state of all the subsequently affected cells in a patient, thus indicating the existence of a distinct mechanism of cellular propagation of the PD-state. We highlight recently published findings on the inter-cellular exchange of mitochondrial DNA and the ability of mitochondrial DNA to modulate the cellular global gene expression state and propose this could form the basis for the inter-cellular transmission of the PD-state.

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Detection of Respiratory Chain Defects in Cultivated Skin Fibroblasts and Skeletal Muscle of Patients with Parkinson's Disease

Cited by 26 publications

References 10 publications

Effect of coenzyme Q10 on the mitochondrial function of skin fibroblasts from Parkinson patients

Effect of coenzyme Q10 on the mitochondrial function of skin fibroblasts from Parkinson patients

Impaired Metabolic Reactivity to Oxidative Stress in Early Psychosis Patients

The universal non-neuronal nature of Parkinson's disease: A theory

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