A5026648305- Alzheimer's disease research and treatments
- Cholinesterase and Neurodegenerative Diseases
- Receptor Mechanisms and Signaling
- Mast cells and histamine
- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Sleep and Wakefulness Research
- Olfactory and Sensory Function Studies
- Environmental Toxicology and Ecotoxicology
- Tryptophan and brain disorders
- Circadian rhythm and melatonin
- Computational Drug Discovery Methods
- Barrier Structure and Function Studies
- Pharmaceutical and Antibiotic Environmental Impacts
- Medicinal Plants and Neuroprotection
- Crystallography and molecular interactions
- S100 Proteins and Annexins
- Neuroendocrine regulation and behavior
- Effects and risks of endocrine disrupting chemicals
- Vector-borne infectious diseases
- Neurological Disease Mechanisms and Treatments
- Toxic Organic Pollutants Impact
- Cerebrospinal fluid and hydrocephalus
- Neurotransmitter Receptor Influence on Behavior
- Mitochondrial Function and Pathology
Centre National de la Recherche Scientifique
2012-2025
Université de Montpellier
2012-2025
Inserm
2012-2025
Université de Nîmes
2017-2024
Institut de Génomique Fonctionnelle
2012-2020
New York University
2009-2016
NYU Langone Health
2010
Yahoo (United Kingdom)
2009
University of Florence
2009
University of Pisa
1998
Alzheimer's disease (AD) is the most common form of dementia affecting 35 million individuals worldwide. Current AD treatments provide only brief symptomatic relief. It therefore urgent to replace this approach with a curative one. Increasing serotonin signaling as well developing molecules that enhance concentration in synaptic cleft have been debated possible therapeutic strategies slow progression AD. In Viewpoint, we discuss exciting new insights regarding modulation for prevention and therapy.
Significance Targeting more than one molecular cause implied in the pathogenesis of Alzheimer’s disease (AD) with a sole drug is considered promising challenge, because it may address numerous failures that recently occurred during clinical trials were conducted this area. Donecopride has been designed by us as multitarget-directed ligand, targeting both serotonin subtype 4 receptor and acetylcholinesterase excellent vitro activities. The latter seems able to not only restore cholinergic...
In this work, we describe the synthesis and in vitro evaluation of a novel series multitarget-directed ligands (MTDL) displaying both nanomolar dual-binding site (DBS) acetylcholinesterase inhibitory effects partial 5-HT4R agonist activity, among which donecopride was selected for further vivo evaluations mice. The latter displayed procognitive antiamnesic enhanced sAPPα release, accounting potential symptomatic disease-modifying therapeutic benefit treatment Alzheimer's disease.
Amyloid β (Aβ) accumulation is considered the main culprit in pathogenesis of Alzheimer's disease (AD). Recent studies suggest that decreasing Aβ production at very early stages AD could be a promising strategy to slow down progression. Serotonin 5-HT4 receptor activation stimulates α-cleavage amyloid precursor protein (APP), leading release soluble and neurotrophic sAPPα fragment thus precluding formation. Using 5XFAD mouse model shows accelerated deposition, we investigated effect chronic...
Abstract Histaminergic neurons of the hypothalamic tuberomammillary nuclei (TMN) send projections to whole brain. Early anatomical studies described histaminergic as a homogeneous cell group, but recent evidence indicates that are heterogeneous and organized into distinct circuits. We addressed this issue using double‐probe microdialysis in freely moving rats investigate if two compounds acting directly onto augment firing [thioperamide bicuculline, histamine H 3 ‐ γ‐aminobutyric acid (GABA)...
After oral administration, the nonimidazole histamine H<sub>3</sub> receptor antagonist, 6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1<i>H</i>-3-benzazepin-7-yl)oxy]-<i>N</i>-methyl-3-pyridinecarboxamide hydrochloride (GSK189254), increased release from tuberomammillary nucleus, where all histaminergic somata are localized, and their axons project to entire brain. To further understand functional circuitry in brain, dual-probe microdialysis was used pharmacologically block receptors monitor...
Amyloid β (Aβ) is the major constituent of brain deposits found in parenchymal plaques and cerebral blood vessels patients with Alzheimer's disease (AD). Several lines investigation support notion that synaptic pathology, one strongest correlates to cognitive impairment, related progressive accumulation neurotoxic Aβ oligomers. Since process oligomerization/fibrillization concentration-dependent, it highly reliant on homeostatic mechanisms regulate steady state levels influencing delicate...
Background and Purpose We recently identified donecopride as a pleiotropic compound able to inhibit AChE activate 5‐HT 4 receptors. Here, we have assessed the potential therapeutic effects of in treating Alzheimer's disease (AD). Experimental Approach used two vivo animal models AD, transgenic 5XFAD mice exposed soluble amyloid‐β peptides and, vitro, primary cultures rat hippocampal neurons. Pro‐cognitive anti‐amnesic were evaluated with novel object recognition, Y‐maze, Morris water maze...
ABSTRACT The gut-brain axis has emerged as a key player in the regulation of brain function and cognitive health. Gut microbiota dysbiosis been observed preclinical models Alzheimer’s disease patients. Manipulating composition gut enhances or delays neuropathology deficits mouse models. Accordingly, health status animal facility may strongly influence these outcomes. In present study, we longitudinally analyzed fecal amyloid pathology 5XFAD mice housed specific opportunistic pathogen-free...
Abstract Cannabinoids exert complex actions on neurotransmitter systems involved in cognition, locomotion, appetite, but no information was available so far the interactions between endocannabinoid system and histaminergic neurons that command several, similar behavioural states memory. In this study, we investigated effect of cannabimimetic compounds histamine release using microdialysis technique brain freely moving rats. We found systemic administration cannabinoid receptors 1 (CB1‐r)...
Remodeling of the brain vasculature is a common trait pathologies. In vivo imaging techniques are fundamental to detect cerebrovascular plasticity or damage occurring overtime and in relation neuronal activity blood flow. two-photon microscopy allows study structural functional large cellular units living brain. particular, thinned-skull window preparation visualization cortical regions interest (ROI) without inducing significant inflammation. Repetitive sessions ROI feasible, providing...
Much has been learned over the past 20 years about role of histamine as a neurotransmitter. This brief article attempts to evaluate progress accomplished in this field, and discusses therapeutic potential H3 receptor (H3R). All histaminergic neurons are localized tuberomammillary nucleus posterior hypothalamus project almost all regions CNS. Histamine exerts its effect via interaction with specific receptors (H1R, H2R, H3R H4R). Antagonists both H1R H2R have successful blockbuster drugs for...