Effect of melatonin administration on the PER1 and BMAL1 clock genes in patients with Parkinson’s disease

Delgado-Lara, Daniela L.C.; González-Enríquez, Gracia Viviana; Torres-Mendoza, Blanca Miriam; González-Usigli, Héctor; Cárdenas-Bedoya, Jhonathan; Macías-Islas, Miguel Ángel; Rosa, Alfredo Celis de la; Jiménez-Delgado, A.; Pacheco-Moisés, Fermín Paul; Serrano, José Antonio Cruz; Ortíz, Genaro Gabriel

doi:10.1016/j.biopha.2020.110485

Cited by 50 publications

(43 citation statements)

References 26 publications

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“…A detailed description of the clinical and sociodemographic characteristics of patients included in this study was previously described [ 11 ]. No serious adverse drug reactions were observed with melatonin at the doses used during the trial and were mild and transitory.…”

Section: Resultsmentioning

confidence: 99%

“…Excluded were patients who had movement disorders other than PD, those with previous thalamotomy, pallidotomy, or deep brain stimulation; pregnant females; and use of alcohol, coffee, or any antioxidant supplement. The design of the study has been previously described [ 11 ].…”

Section: Methodsmentioning

confidence: 99%

“…The placebo-melatonin group received initial placebo during 3 months followed by a washout period and then received melatonin. This melatonin administration dosage and schedule were used in a previous clinical trial of our research group in which the expression of two clock genes (PER1 and BMAL1) were assessed and in which no adverse effects were observed except daytime sleepiness and nighttime problems [ 11 ]. Additionally, a control group of thirty clinically healthy individuals was also included to compare the baseline values of the oxidative stress markers and enzymatic activity analyzed in this study.…”

Section: Methodsmentioning

confidence: 99%

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Effect of Melatonin Administration on Mitochondrial Activity and Oxidative Stress Markers in Patients with Parkinson’s Disease

Jiménez-Delgado

Ortíz

Delgado-Lara

et al. 2021

Oxidative Medicine and Cellular Longevity

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Mitochondrial dysfunction and oxidative stress are extensively linked to Parkinson’s disease (PD) pathogenesis. Melatonin is a pleiotropic molecule with antioxidant and neuroprotective effects. The aim of this study was to evaluate the effect of melatonin on oxidative stress markers, mitochondrial complex 1 activity, and mitochondrial respiratory control ratio in patients with PD. A double-blind, cross-over, placebo-controlled randomized clinical trial study was conducted in 26 patients who received either 25 mg of melatonin or placebo at noon and 30 min before bedtime for three months. At the end of the trial, in patients who received melatonin, we detected a significant diminution of lipoperoxides, nitric oxide metabolites, and carbonyl groups in plasma samples from PD patients compared with the placebo group. Conversely, catalase activity was increased significantly in comparison with the placebo group. Compared with the placebo group, the melatonin group showed significant increases of mitochondrial complex 1 activity and respiratory control ratio. The fluidity of the membranes was similar in the melatonin group and the placebo group at baseline and after three months of treatment. In conclusion, melatonin administration was effective in reducing the levels of oxidative stress markers and restoring the rate of complex I activity and respiratory control ratio without modifying membrane fluidity. This suggests that melatonin could play a role in the treatment of PD.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Melatonin Administration on Mitochondrial Activity and Oxidative Stress Markers in Patients with Parkinson’s Disease

Jiménez-Delgado

Ortíz

Delgado-Lara

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…PER1 has a role in feeding and active behavior in mammals and is controlled by circadian rhythms (Kim et al, 2020). From a non-tumor perspective, PER1 is related to conditions such as Parkinson's disease, obesity, sleep, drug resistance, and premature ovarian insufficiency (Zheng et al, 2019;Delgado-Lara et al, 2020;EmeklI et al, 2020;Mabrouk et al, 2020;Arellanes-Licea et al, 2021). PER1 enhances the activity of GPX through the interaction of PER1 and GPX1 in the cytoplasm, thereby improving the oxidative phosphorylation efficiency of mitochondria (Sun et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

PER1 Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Ovarian Cancer

et al. 2021

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Background: Period circadian protein homolog 1 (PER1) is an important component of the biorhythm molecular oscillation system and plays an important part in the development and progression of mammalian cancer. However, the correlations of PER1 with prognosis and tumor-infiltrating lymphocytes in ovarian cancer (OV) remain unclear.Methods: The Oncomine and TIMER databases were used to examine the expression of PER1 in OV. Kaplan–Meier Plotter and PrognoScan were used to evaluate the relationship between PER1 and prognosis. Kaplan–Meier Plotter was used to analyze the relationships between PER1 and clinicopathological features of OV patients. The relationship between PER1 expression and immune infiltration in OV was investigated using the TIMER database and CIBERSORT algorithm. The STRING database was used to analyze PER1-related protein functional groups, the GeneMANIA online tool was used to analyze gene groups with similar functions to those of PER1, and Network Analyst was used to identify transcription factors that regulate PER1. The correlation between PER1 and immunoinvasion of OV was analyzed using TIMER. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect PER1 expression.Results: PER1 was differentially expressed in different cancer tissues, and its expression in various OV subtypes was lower than that in normal ovarian tissue. OV patients with low PER1 expression had a reduced overall survival rate. Decreased PER1 expression in stage 1 and stage 1+2 OV patients was related to poor prognosis, while increased PER1 expression in stage 3+4 patients and TP53 mutation were related to poor overall survival and progression-free survival. We identified eight genes whose expression was strongly correlated with that of PER1, as well as four transcription factors that regulate PER1. In OV, PER1 expression levels were positively correlated with infiltration levels of cells including neutrophils, regulatory T cells, and M2 macrophages, and closely related to a variety of immune markers. Reduced expression of PER1 was significantly associated with poor overall survival.Conclusion: These findings suggest that PER1 could be used as a prognostic biomarker to determine prognosis and immune infiltration in OV patients.

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“…To date, ageing and neurodegenerative diseases, such as Alzheimer's (AD) or Parkinson's diseases linked to ageing, are ever‐increasing due to the global demographic changes 1,2 . The cognitive decline represents a serious hindrance to achieving a long and healthy life.…”

Section: Introductionmentioning

confidence: 99%

Lamivudine improves cognitive decline in SAMP8 mice: Integrating in vivo pharmacological evaluation and network pharmacology

Zhao

Tang

et al. 2021

J Cellular Molecular Medi

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The reverse transcriptase inhibitors such as lamivudine (3TC) play important roles in anti‐ageing, but their effects on neurodegenerative diseases caused by ageing are not clear, especially on the functions of the nervous system such as cognition. In this study, we administered 3TC to senescence‐accelerated mouse prone 8 (SAMP8) mice by gastric perfusion (100 mg/kg) for 4 weeks. Our results showed that 3TC significantly improved the ageing status of SAMP8 mice, especially the decline of cognitive ability evaluated by the Morris water maze test. To further investigate the molecular mechanisms of improving the ageing status of SAMP8 mice by 3TC, the qPCR and tissue staining methods were used to study the brain tissues (i.e., hippocampus and cortex) of mice, while the network pharmacology analysis was applied to investigate the potential targets of 3TC. The results showed that the mRNA levels of genes related to long interspersed element‐1, type 1 interferon response, the senescence‐associated secretion phenotype and the Alzheimer's disease in the hippocampus and cortex of SAMP8 mice were increased due to senescence, but this trend was reversed partially by 3TC. Results of histological studies showed that 3TC reduced the death of hippocampal neurons, while the results of network pharmacology analysis indicated that 3TC may exert its influence through multiple pathways, including the oestrogen signalling and the PI3K/Akt and neuroactive ligand‐receptor interaction signalling pathways, which we have verified through in vitro experiments. These findings provide evidence for the therapeutic potential of 3TC in the treatment of neurodegenerative diseases.

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Effect of melatonin administration on the PER1 and BMAL1 clock genes in patients with Parkinson’s disease

Cited by 50 publications

References 26 publications

Effect of Melatonin Administration on Mitochondrial Activity and Oxidative Stress Markers in Patients with Parkinson’s Disease

Effect of Melatonin Administration on Mitochondrial Activity and Oxidative Stress Markers in Patients with Parkinson’s Disease

PER1 Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Ovarian Cancer

Lamivudine improves cognitive decline in SAMP8 mice: Integrating in vivo pharmacological evaluation and network pharmacology

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