A5058763931- Neuroinflammation and Neurodegeneration Mechanisms
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Nicotinic Acetylcholine Receptors Study
- Cholinesterase and Neurodegenerative Diseases
- Alzheimer's disease research and treatments
- Inflammation biomarkers and pathways
- Organophosphorus compounds synthesis
- Neurological Disease Mechanisms and Treatments
- Crystallography and molecular interactions
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Immune cells in cancer
- Tryptophan and brain disorders
- Receptor Mechanisms and Signaling
- Nuclear Receptors and Signaling
- Neurotransmitter Receptor Influence on Behavior
- Adipokines, Inflammation, and Metabolic Diseases
- Autophagy in Disease and Therapy
- Neuroscience and Neuropharmacology Research
- Nerve injury and regeneration
- Circular RNAs in diseases
- Atherosclerosis and Cardiovascular Diseases
- Extracellular vesicles in disease
- Chemical synthesis and alkaloids
- Fluorine in Organic Chemistry
Universitat de Barcelona
2018-2025
University College London
2024
National Hospital for Neurology and Neurosurgery
2024
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...
Behavioural and psychological symptoms of dementia (BPSD) are presented in 95% Alzheimer’s Disease (AD) patients also associated with neurotrophin deficits. The molecular mechanisms leading to age-related diseases still unclear; however, emerging evidence has suggested that epigenetic modulation is a key pathophysiological basis ageing neurodegeneration. In particular, it been G9a methyltransferase its repressive histone mark (H3K9me2) important shaping learning memory by modulating...
The development of effective therapeutic strategies against Alzheimer's disease (AD) remains a challenge. I2 imidazoline receptor ligands have neuroprotective role in AD. Moreover, co-treatment AChE inhibitors with agents shown better effects on the prevention dementia. Here, we assessed potential effect ligand, donepezil and their combination 5XFAD mice.5XFAD female mice were treated low doses (1 mg·kg-1 ·day-1 ) LSL60101, plus during 4 weeks per os. Novel object recognition, Morris water...
Imidazoline I2 receptors (I2-IR), widely distributed in the CNS and altered patients that suffer from neurodegenerative disorders, are orphans a structural point of view, new I2-IR ligands urgently required for improving their pharmacological characterization. We report synthesis three-dimensional quantitative structure–activity relationship (3D-QSAR) studies family bicyclic α-iminophosphonates endowed with relevant affinities human brain I2-IR. Acute treatment mice selected compound...
Recent findings unveil the pharmacological modulation of imidazoline I2 receptors (I2-IR) as a novel strategy to face unmet medical neurodegenerative diseases. In this work, we report chemical characterization, three-dimensional quantitative structure-activity relationship (3D-QSAR) and ADMET in silico family benzofuranyl-2-imidazoles that exhibit affinity against human brain I2-IR most them have been predicted be permeable. Acute treatment mice with 2-(2-benzofuranyl)-2-imidazole, known...
Behavioural and psychological symptoms of dementia (BPSD), including fear-anxiety- depressive-like behaviour, are present in Alzheimer's disease (AD), together with memory decline. I2-imidazoline receptors (I2-IRs) have been associated neuropsychiatric neurodegenerative disorders, further, I2-IR ligands demonstrated a neuroprotective role the central nervous system (CNS). In this study, we assessed effect ligand MCR5 on both cognitive non-cognitive Senescence accelerated mice prone 8 (SAMP8)...
Abstract Classic immunometabolic switching from oxidative phosphorylation (OXPHOS) to glycolysis occurs in myeloid cells such as microglia when encountering pathogenic insults. We previously showed that patient iPSC-derived (iPS-Mg) harbouring the Alzheimer’s disease (AD) TREM2 R47H hypomorph display deficits ability metabolically switch OXPHOS glycolysis, with both reduced mitochondrial maximal respiration and glycolytic capacity. To resolve this, we generated common variant, −/− variant...
<title>Abstract</title> In Alzheimer’s disease (AD) and multiple sclerosis (MS), microglia are exposed to the blood protein fibrinogen (FG), we showed previously response of primary-cultured rat FG. Here, show human iPSC-derived (iPS-Mg) respond FG, inducing secretion a range cytokines chemokines activation stress pathways. An increased pro-caspase 4/5 (and active caspase-4/5) expression was independent ER stress. Furthermore, unlike LPS/ATP which led canonical NLRP3 inflammasome pathway...
The microglial triggering receptor expressed on myeloid cells 2 (TREM2) is required for diverse microglia responses in neurodegeneration, including immunometabolic plasticity, phagocytosis, and survival. We previously identified that patient iPSC‐derived (iPS‐Mg) harboring the Alzheimer's disease (AD) TREM2 R47H hypomorph display several functional deficits linked to metabolism. To investigate whether these are associated with disruptions metabolite signaling, we generated common variant,...
Alzheimer&rsquo;s disease (AD) is characterized by cognitive impairment and different non-cognitive deficits called &ldquo;Behavioural psychological symptoms of dementia&rdquo; (BPSD) related to neurotrophin alterations, which differ from those presented in normal aging. Mouse models, both transgenics inbreed mice models AD, are a useful tool understanding the underlying mechanisms disease. The SAMP8 (senescence-accelerated mouse prone 8) line was generated AKR/J strain Professor...
I2-IR have been found dysregulated in patients with neurodegenerative diseases, such as Alzheimer's disease (AD), which the importance of neuroinflammation establishment and maintenance cognitive decline is well-documented. To research implication neuroinflammatory pathways altered AD, we determined expression profile genes associated inflammation 5XFAD model treated LSL60101, a well-established ligand. Thus, performed qPCR array containing 84 inflammation-related genes. Hierarchical...