An omics-based strategy using coenzyme Q10 in patients with Parkinson’s disease: concept evaluation in a double-blind randomized placebo-controlled parallel group trial

Prasuhn, Jannik; Brüggemann, Norbert; Heßler, Nicole; Berg, Daniela; Gasser, Thomas; Brockmann, Kathrin; Olbrich, Denise; Ziegler, Andreas; König, Inke R.; Klein, Christine; Kasten, Meike

doi:10.1186/s42466-019-0033-1

Cited by 35 publications

(44 citation statements)

References 13 publications

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“…Strategies to improve mitochondrial function have been under consideration for the treatment of neurological and psychiatric disorders for quite some time, with limited success in clinical trials [ 271 , 272 , 273 , 274 , 275 ], despite promising results in animal models [ 276 , 277 , 278 , 279 , 280 , 281 ]. Even in individuals with genetic mutations that cause mitochondrial dysfunction and multi-organ disease, there are few treatment options [ 282 ].…”

Section: Viable Avenues For Drug Discovery and Therapeutic Intervementioning

confidence: 99%

Dysregulation of PGC-1α-Dependent Transcriptional Programs in Neurological and Developmental Disorders: Therapeutic Challenges and Opportunities

McMeekin

Fox

Boas

et al. 2021

Cells

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Substantial evidence indicates that mitochondrial impairment contributes to neuronal dysfunction and vulnerability in disease states, leading investigators to propose that the enhancement of mitochondrial function should be considered a strategy for neuroprotection. However, multiple attempts to improve mitochondrial function have failed to impact disease progression, suggesting that the biology underlying the normal regulation of mitochondrial pathways in neurons, and its dysfunction in disease, is more complex than initially thought. Here, we present the proteins and associated pathways involved in the transcriptional regulation of nuclear-encoded genes for mitochondrial function, with a focus on the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α). We highlight PGC-1α’s roles in neuronal and non-neuronal cell types and discuss evidence for the dysregulation of PGC-1α-dependent pathways in Huntington’s Disease, Parkinson’s Disease, and developmental disorders, emphasizing the relationship between disease-specific cellular vulnerability and cell-type-specific patterns of PGC-1α expression. Finally, we discuss the challenges inherent to therapeutic targeting of PGC-1α-related transcriptional programs, considering the roles for neuron-enriched transcriptional coactivators in co-regulating mitochondrial and synaptic genes. This information will provide novel insights into the unique aspects of transcriptional regulation of mitochondrial function in neurons and the opportunities for therapeutic targeting of transcriptional pathways for neuroprotection.

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Section: Viable Avenues For Drug Discovery and Therapeutic Intervementioning

confidence: 99%

Dysregulation of PGC-1α-Dependent Transcriptional Programs in Neurological and Developmental Disorders: Therapeutic Challenges and Opportunities

McMeekin

Fox

Boas

et al. 2021

Cells

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“…After that, a more extensive study was performed with early PD-diagnosed patients, who were treated with doses up to 1200 mg per day, showing that CoQ10 was safe and well-tolerated and delayed the progressive function deterioration [ 69 ]. From these studies, doses and number of patients have been modified; however, the effects of preclinical trials have not been reproduced [ 70 , 71 , 72 , 73 ].…”

Section: Mitochondria-targeted Antioxidants Therapeutic Effect Onmentioning

confidence: 99%

Antioxidant Therapeutics in Parkinson’s Disease: Current Challenges and Opportunities

et al. 2021

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Oxidative stress is considered one of the pathological mechanisms that cause Parkinson’s disease (PD), which has led to the investigation of several antioxidants molecules as a potential therapeutic treatment against the disease. Although preclinical studies have demonstrated the efficacy of these compounds to maintain neuronal survival and activity in PD models, these results have not been reflected in clinical trials, antioxidants have not been able to act as disease modifiers in terms of clinical symptoms. Translational medicine currently faces the challenge of redesigning clinical trials to standardize criteria when testing molecules to reduce responses’ variability. Herein, we discuss current challenges and opportunities regarding several non-enzymatic antioxidants’ therapeutic molecules for PD patients’ potential treatment.

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“…Studies in flies identified vitamin k2 as an alternative electron carrier molecule that similar to ubiquinone can stimulate the ETC resulting in a rescue of Pink1-related phenotypes [ 27 ], nominating it to be a promising therapeutic strategy in the treatment of PINK1-related PD patients. The application of ubiquinone and vitamin k2 as therapy in patients has been initiated in clinical trials [ 98 , 99 ] and serves as an excellent example of therapeutic targets identified in flies that are now being tested in patients.…”

Section: The Mitochondrial-pd Connection In Drosophila Mmentioning

confidence: 99%

The Importance of Drosophila melanogaster Research to UnCover Cellular Pathways Underlying Parkinson’s Disease

Vos

Klein

2021

Cells

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Parkinson’s disease (PD) is a complex neurodegenerative disorder that is currently incurable. As a consequence of an incomplete understanding of the etiology of the disease, therapeutic strategies mainly focus on symptomatic treatment. Even though the majority of PD cases remain idiopathic (~90%), several genes have been identified to be causative for PD, facilitating the generation of animal models that are a good alternative to study disease pathways and to increase our understanding of the underlying mechanisms of PD. Drosophila melanogaster has proven to be an excellent model in these studies. In this review, we will discuss the different PD models in flies and key findings identified in flies in different affected pathways in PD. Several molecular changes have been identified, of which mitochondrial dysfunction and a defective endo-lysosomal pathway emerge to be the most relevant for PD pathogenesis. Studies in flies have significantly contributed to our knowledge of how disease genes affect and interact in these pathways enabling a better understanding of the disease etiology and providing possible therapeutic targets for the treatment of PD, some of which have already resulted in clinical trials.

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An omics-based strategy using coenzyme Q10 in patients with Parkinson’s disease: concept evaluation in a double-blind randomized placebo-controlled parallel group trial

Cited by 35 publications

References 13 publications

Dysregulation of PGC-1α-Dependent Transcriptional Programs in Neurological and Developmental Disorders: Therapeutic Challenges and Opportunities

Dysregulation of PGC-1α-Dependent Transcriptional Programs in Neurological and Developmental Disorders: Therapeutic Challenges and Opportunities

Antioxidant Therapeutics in Parkinson’s Disease: Current Challenges and Opportunities

The Importance of Drosophila melanogaster Research to UnCover Cellular Pathways Underlying Parkinson’s Disease

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