A5048967154- Neuroinflammation and Neurodegeneration Mechanisms
- Epigenetics and DNA Methylation
- Alzheimer's disease research and treatments
- Eicosanoids and Hypertension Pharmacology
- Tryptophan and brain disorders
- Sirtuins and Resveratrol in Medicine
- Histone Deacetylase Inhibitors Research
- Adipose Tissue and Metabolism
- X-ray Diffraction in Crystallography
- Cholinesterase and Neurodegenerative Diseases
- Crystallization and Solubility Studies
- Biochemical effects in animals
- Biochemical Acid Research Studies
- Hormonal Regulation and Hypertension
- Genetics, Aging, and Longevity in Model Organisms
- Stress Responses and Cortisol
- Diet and metabolism studies
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Autophagy in Disease and Therapy
- GDF15 and Related Biomarkers
- Click Chemistry and Applications
- Synthesis and biological activity
- MicroRNA in disease regulation
- Birth, Development, and Health
Universitat de Barcelona
2016-2025
Biomedical Research Networking Center on Neurodegenerative Diseases
2017-2025
Instituto de Salud Carlos III
2023-2025
Institut de Biomedicina de la Universitat de Barcelona
2021
The amyloid-β protein precursor/presenilin 1 (AβPP/PS1) mouse model of Alzheimer's disease (AD) has provided robust neuropathological hallmarks familial AD-like pattern. AD is a neurodegenerative process that causes severe cognitive impairment; it
5XFAD is an early-onset mouse transgenic model of Alzheimer disease (AD). Up to now there are no studies that focus on the epigenetic changes produced as a result Aβ-42 accumulation and possible involvement in different expression related AD-genes. Under several behavioral cognition test, we found impairment memory psychoemotional female mice reference wild type worsens with age.Cognitive correlated alterations protein level analysis gene markers tau aberrant phosphorylation, amyloidogenic...
Cumulative evidence shows that modifications in lifestyle factors constitute an effective strategy to modulate molecular events related neurodegenerative diseases, confirming the relevant role of epigenetics. Accordingly, Environmental Enrichment (EE) represents approach ameliorate cognitive decline and neuroprotection Alzheimer's disease (AD). AD is characterized by specific neuropathological hallmarks, such as β-amyloid plaques Neurofibrillary Tangles, which severely affect areas brain...
With innumerable clinical failures of target-specific drug candidates for multifactorial diseases, such as Alzheimer's disease (AD), which remains inefficiently treated, the advent multitarget discovery has brought a new breath hope. Here, we disclose class 6-chlorotacrine (huprine)-TPPU hybrids dual inhibitors enzymes soluble epoxide hydrolase (sEH) and acetylcholinesterase (AChE), profile to provide cumulative effects against neuroinflammation memory impairment. Computational studies...
Epigenetic alterations are a fundamental pathological hallmark of Alzheimer’s disease (AD). Herein, we show the upregulation G9a and H3K9me2 in brains AD patients. Interestingly, treatment with inhibitor (G9ai) SAMP8 mice reversed high levels rescued cognitive decline. A transcriptional profile analysis after G9ai revealed increased gene expression glia maturation factor β (GMFB) mice. Besides, ChIP-seq inhibition showed enrichment promoters associated neural functions. We observed induction...
About 80% of brain disorders have a genetic basis. The pathogenesis most neurodegenerative diseases is associated with myriad defects, epigenetic alterations (DNA methylation, histone/chromatin remodeling, miRNA dysregulation), and environmental factors. emergence new sequencing technologies tools to study the epigenome has led identifying predictive biomarkers for earlier diagnosis, opening up possibility prophylactical interventions. As result, advances in pharmacogenetics...
Melatonin is an endogenous pleiotropic molecule which orchestrates regulatory functions and protective capacity against age-related ailments. The increase in circulating levels of melatonin through dietary supplements intensifies its health benefits. Investigations animal models have shown that protects Alzheimer's disease (AD)-like pathology, although clinical studies not been conclusive. We hypothesized induces changes the brain prevent or attenuate AD by increasing resilience. Therefore,...
With the increase in life expectancy, aging and age-related cognitive impairments are becoming one of most important issues for human health. At same time, it has been shown that epigenetic mechanisms emerging as universally factors expectancy. The Senescence Accelerated Mouse P8 (SAMP8) strain exhibits deterioration evidenced learning memory abilities is a useful model neurodegenerative disease. In SAMP8, Environmental Enrichment (EE) increased DNA-methylation levels (5-mC) reduced...
The implication of epigenetic mechanisms in Alzheimer's disease (AD) has been demonstrated several studies.UNC0642, a specific and potent inhibitor methyltransferase activity G9a/GLP (G9a-like) complex, was evaluated the 5XFAD mouse model.UNC0642 treatment rescued cognition impairment, reduced DNAmethylation (5-mC), increased hydroxymethylation (5-hmC), decreased di-methylation lysine 9 histone H3 (H3K9me2) levels hippocampus.Increases Nuclear Factor erythroid-2-Related 2 (NRF2), Heme...
Alzheimer's disease (AD) is the leading cause of dementia. Non-competitive N-Methyl-D-aspartate (NMDA) receptor antagonist memantine improved cognition and molecular alterations after preclinical treatment. Nevertheless, clinical results are discouraging. In vivo efficacy RL-208, a new NMDA blocker described recently, with favourable pharmacokinetic properties was evaluated in Senescence accelerated mice prone 8 (SAMP8), model late-onset AD (LOAD). Oral administration RL-208 cognitive...
Inflammation and oxidative stress (OS) are key points in age progression. Both processes impact negatively cognition brain functions. Resveratrol (RV) has been postulated as a potent antioxidant natural compound, with rejuvenating properties. Inducing metabolic by high-fat (HF) diet aged C56/BL6 (24 months) led to cognitive disturbances compared control mated young mice. These changes were prevented RV. Molecular determinations demonstrated significant increase some inflammatory parameters...
Transcription disequilibria are characteristic of many neurodegenerative diseases. The activity-evoked transcription immediate early genes (IEGs), important for neuronal plasticity, memory and behavior, is altered in CNS diseases governed by epigenetic modulation. KDM1A, a histone 3 lysine 4 demethylase that forms part regulation complexes, has been implicated the control IEG transcription. Here we report development vafidemstat (ORY-2001), brain penetrant inhibitor KDM1A MAOB. ORY-2001...
A variety of environmental factors contribute significantly to age-related cognitive decline and memory impairment in Alzheimer's Disease (AD) other neurodegenerative diseases. Nutrition can alter epigenetics, improving health outcomes, which be transmitted across generations; this process is called epigenetic inheritance. We investigate the beneficial effects maternal resveratrol supplementation direct exposed F1 generation transgenerational F2 generation. The offspring was generated from...
Environmental factors such as maternal high-fat diet (HFD) intake can increase the risk of age-related cognitive decline in adult offspring. Epigenetic mechanisms are a possible link between effect and neurodegeneration across generations. Here, we found significant decrease triglyceride levels with resveratrol (RSV) HFD + RSV group Firstly, obtained better performance HFD+RSV groups their Molecularly, DNA methylation (5-mC) levels, well increased gene expression methyltransferase 1 (Dnmt1)...
Overstimulation of N-methyl-D-aspartate receptors (NMDARs) is the leading cause brain excitotoxicity and often contributes to neurodegenerative diseases such as Alzheimer's Disease (AD), most common form dementia. This study aimed evaluate a new NMDA receptor antagonist (UB-ALT-EV) memantine in 6-month-old female 5XFAD mice that were exposed orally chronic low-dose treatment. Behavioral cognitive tests confirmed better performance both treated groups. Calcium-dependent protein calpain-1...
ABSTRACT This review provides a comprehensive overview of the role G9a/EHMT2, focusing on its structure and exploring impact pharmacological and/or gene inhibition in various neurological diseases. In addition, we delve into advancements design synthesis G9a/EHMT2 inhibitors, which hold promise not only as treatment for neurodegeneration diseases but also other conditions, such cancer malaria. Besides, presented discovery dual therapeutic approaches based G9a different epigenetic enzymes...
Imidazoline I2 receptors (I2-IRs) are altered in Alzheimer's disease (AD) patients and associated with analgesia. I2-IRs not structurally described, their pharmacological characterization relies on modulation by highly affine ligands. Herein, we describe the synthesis of (3-phenylcarbamoyl-3,4-dihydro-2H-pyrrol-2-yl)phosphonates endowed relevant affinities for human brain tissues. The optimal ADME pharmacokinetic profile a selected compound, 12d, secured its vivo exploration senescence...