A5086149472- Circadian rhythm and melatonin
- Autophagy in Disease and Therapy
- Parkinson's Disease Mechanisms and Treatments
- Mitochondrial Function and Pathology
- Alzheimer's disease research and treatments
- Tryptophan and brain disorders
- Migraine and Headache Studies
- Nitric Oxide and Endothelin Effects
- Zebrafish Biomedical Research Applications
- Stress Responses and Cortisol
- Genetics, Aging, and Longevity in Model Organisms
- Ophthalmology and Eye Disorders
- Synthesis of heterocyclic compounds
- Spondyloarthritis Studies and Treatments
- Tuberculosis Research and Epidemiology
- MicroRNA in disease regulation
- Synthesis of Organic Compounds
- Birth, Development, and Health
- Neurological diseases and metabolism
- Crystallization and Solubility Studies
- Heart Rate Variability and Autonomic Control
- Photoreceptor and optogenetics research
- Organic Chemistry Cycloaddition Reactions
- Rheumatoid Arthritis Research and Therapies
- Electron Spin Resonance Studies
University of Cambridge
2017-2025
UK Dementia Research Institute
2022-2025
Universidade de Santiago de Compostela
1993-2019
Ikerbasque
2019
Weatherford College
2019
CIC biomaGUNE
2019
Wellcome Trust
2017-2018
Hospital General de México
2015-2018
Universidad de Granada
2007-2017
Parque Tecnológico de la Salud
2008-2017
We studied the subcellular levels of melatonin in cerebral cortex and liver rats under several conditions. The results show that cell membrane, cytosol, nucleus, mitochondrion vary over a 24-hr cycle, although these variations do not exhibit circadian rhythms. membrane has highest concentration followed by mitochondria, cytosol. Pinealectomy significantly increased content all compartments, whereas luzindole treatment had little effect on levels. Administration 10 mg/kg bw to...
The role of melatonin in improving mitochondrial respiratory chain activity and increasing ATP production different experimental conditions has been widely reported. To date, however, the mechanism(s) involved are largely unknown. Using high-resolution respirometry, fluorometry spectrophotometry we studied effects on normal functions. Mitochondria were recovered from mouse liver cells incubated vitro with at concentrations ranging 1 nm to mm. Melatonin decreased oxygen consumption...
Mucositis is a common and distressing side effect of chemotherapy or radiotherapy that has potentially severe consequences, no treatment available. The purpose this study was to analyze the molecular pathways involved in development oral mucositis evaluate whether melatonin can prevent pathology. tongue male Wistar rats subjected irradiation (X-ray YXLON Y.Tu 320-D03 irradiator; animals received dose 7.5 Gy/day for 5 days). Rats were treated with 45 mg/day vehicle 21 days postirradiation,...
Neurodegenerative diseases like Alzheimer's disease, Parkinson's disease and Huntington's manifest with the neuronal accumulation of toxic proteins. Since autophagy upregulation enhances clearance such proteins ameliorates their toxicities in animal models, we others have sought to re-position/re-profile existing compounds used humans identify those that may induce brain. A key challenge this approach is assess if any hits identified can at concentrations would be seen taking drug for its...
Mutations in the gene encoding tau (MAPT) cause frontotemporal dementia spectrum disorders. A rare variant p.A152T was reported as a risk factor for and Alzheimer's disease an initial case-control study. Such findings need replication independent cohort. We analysed multinational cohort comprising 3100 patients with neurodegenerative 4351 healthy control subjects found associated significantly higher clinically defined progressive supranuclear palsy syndrome. To assess functional biochemical...
Abstract β-Propeller protein-associated neurodegeneration (BPAN) is a rare X-linked dominant disease, one of several conditions that manifest with and brain iron accumulation. Mutations in the WD repeat domain 45 ( WDR45 ) gene encoding WIPI4 lead to loss function BPAN but cellular mechanisms how these trigger pathology are unclear. The prevailing view literature simply consequence autophagy deficiency given functions this degradation pathway. However, our data indicate depletion causes...
The existence of an inducible mitochondrial nitric oxide synthase has been recently related to the nitrosative/oxidative damage and dysfunction that occurs during endotoxemia. Melatonin inhibits both activities, a finding antiseptic properties indoleamine. Hence, we examined changes in synthase/inducible expression activity, bioenergetics oxidative stress heart mitochondria following cecal ligation puncture-induced sepsis wild-type (iNOS(+/+)) synthase-deficient (iNOS(-/-)) mice. We also...
It is hypothesized that, besides increased free radical production, aging a process also related to inflammation. Thus, female and male senescence-accelerated (SAMP8) senescence-resistant (SAMR1) mice of 5 10 months age were studied assess this hypothesis. Plasma from these was processed determine nitric oxide (NO), pro-inflammatory [interleukin (IL)-1beta, IL-2, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, granulocyte-macrophage colony-stimulating factor] anti-inflammatory...
Abstract: The antiproliferative and proapoptotic properties of melatonin in human colon cancer cells culture were recently reported. To address the mechanisms involved these actions, HT‐29 cultured RPMI 1640 medium supplemented with fetal bovine serum at 37°C. Cell proliferation was assessed by incorporation [ 3 H]‐thymidine into DNA. Cyclic nucleotide levels, nitrite concentration, glutathione peroxidase reductase activities, levels after incubation following drugs: membrane receptor...
Melatonin prevents mitochondrial failure in models of sepsis through its ability to inhibit the expression and activity both cytosolic (iNOS) (i-mtNOS) inducible nitric oxide synthases. Because Parkinson's disease (PD), like sepsis, is associated with iNOS induction, we assessed existence changes iNOS/i-mtNOS their relation dysfunction MPTP model PD, which also displays increased expression. We evaluated role melatonin (aMT) brain metabolite, N(1)-acetyl-5-methoxykynuramine (AMK), preventing...
Coenzyme Q10 (CoQ10) or ubiquinone is a well-known component of the mitochondrial respiratory chain. In humans, CoQ10 deficiency causes syndrome with an unexplained variability in clinical presentations. To try to understand this heterogeneity phenotypes, we have generated Coq9 Knockin (R239X) mouse model. The lack functional protein homozygous mutant (Coq9X/X) mice severe reduction Coq7 and, as consequence, widespread CoQ and accumulation demethoxyubiquinone. deficit induces brain-specific...
Abstract While it is accepted that the high production of nitric oxide ( NO ˙) by inducible synthase iNOS ) impairs cardiac mitochondrial function during sepsis, role neuronal nNOS may be protective. During there a significantly increase in expression and activity (i‐mt NOS ), which parallels changes cytosolic . The existence constitutive form (c‐mt heart mitochondria has been also described, but its failure sepsis remains unclear. Herein, we analyzed oxidative stress bioenergetics wild‐type...
To study iron deposition in red nucleus (RN), globus pallidus (GP), and periaqueductal gray matter (PAG) as a potential biomarker of chronic migraine (CM) its association with levels biomarkers related to pathophysiology.This case-control included 112 patients (55 CM, 57 episodic [EM]) 25 headache-free controls. We analyzed using 3T MRI the NIH software platform ImageJ; we serum markers inflammation, endothelial dysfunction, blood-brain barrier (BBB) disruption by ELISA peripheral blood...
Objective The aim of this study is to find a relation between several biomarkers in peripheral blood and outcome after treatment with onabotulinumtoxin A (OnabotA). Background OnabotA an effective chronic migraine (CM). Different studies have tried predictors response treatment, either clinical characteristics, neuroimaging features, or molecular biomarkers; however, it still not possible predict the individual outcome. Methods We measured serum levels inflammation (IL‐6, IL‐10, TNF‐α,...
The COVID-19 has originated from Wuhan, China, in December 2019 and been affecting the public health system, society, economy an unheard-of manner. There is no specific treatment or vaccine available for COVID-19. Previous data showed that men are more affected than women by COVID-19, then we hypothesized whether sex hormones could be protecting female organism against infection. VERO E6 cells have commonly used as vitro model SARS-CoV-2 In our experimental approach, treated with...
Cardiac and diaphragmatic mitochondria from male SAMP8 (senescent) SAMR1 (resistant) mice of 5 or 10 months age were studied. Levels lipid peroxidation (LPO), glutathione (GSH), GSH disulfide (GSSG), peroxidase reductase (GRd) activities measured. In addition, the effect chronic treatment with antioxidant melatonin 1 to was evaluated. show an age-dependent increase in LPO levels a reduction GSH:GSSG ratios. Chronic counteracted ratio these mitochondria. Melatonin also increased GRd activity,...
Background: The antioxidant and anti‐inflammatory hormone melatonin is secreted by saliva into the oral cavity, where it may protect mucosal gingival tissues from radical damage. To date, no studies have addressed potential beneficial role of in acute inflammatory response that follows surgical interventions, especially tooth extractions. aim this study was to determine whether extraction induces changes plasma oxidative stress levels, treatment counteract these changes. Methods: Maxillary...