A5027693550- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Supramolecular Self-Assembly in Materials
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Prion Diseases and Protein Misfolding
- Protein Structure and Dynamics
- RNA Interference and Gene Delivery
- Neurological disorders and treatments
- Telomeres, Telomerase, and Senescence
- Extracellular vesicles in disease
- Lipid Membrane Structure and Behavior
- COVID-19 Impact on Reproduction
- Signaling Pathways in Disease
- Drug Transport and Resistance Mechanisms
- Medicinal Plants and Neuroprotection
- Neurotransmitter Receptor Influence on Behavior
- Olfactory and Sensory Function Studies
- MicroRNA in disease regulation
- RNA regulation and disease
- Advanced Glycation End Products research
- Biotin and Related Studies
- Parkinson's Disease Mechanisms and Treatments
de Duve Institute
2022-2023
UCLouvain
2020-2021
Universitat de Barcelona
2014-2018
Centro de Investigación Biomédica en Red
2017
Instituto de Salud Carlos III
2017
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2014-2015
Biomedical Research Networking Center on Neurodegenerative Diseases
2014-2015
Learning and memory deficits are early clinical manifestations of Huntington's disease (HD). These cognitive impairments have been mainly associated with frontostriatal HD pathology; however, compelling evidence provided by several murine models suggests that the hippocampus may contribute to synaptic dysfunction in HD. The neurotrophin receptor p75(NTR) negatively regulates spine density, which is learning memory; therefore, we explored whether disturbed function could Here, determined...
Abstract Huntington’s disease (HD) is a neurodegenerative disorder whose major symptoms include progressive motor and cognitive dysfunction. Cognitive decline critical quality of life concern for HD patients families. The enzyme histone deacetylase 3 (HDAC3) appears to be important in pathology by negatively regulating genes involved functions. Furthermore, HDAC3 has been implicated the aberrant transcriptional patterns that help cause mice. also helps fuel CAG repeat expansions human cells,...
Abstract Aging is the main risk factor for Alzheimer’s disease (AD) and other neurodegenerative pathologies, but molecular cellular changes underlying pathological aging of nervous system are poorly understood. AD pathology seems to correlate with appearance cells that become senescent due progressive accumulation insults causing DNA damage. Senescence has also been shown reduce autophagic flux, a mechanism involved in clearing damaged proteins from cell, such impairment linked pathogenesis....
The dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine endocannabinoid receptors present in striatum, ie, A2A receptor (A2AR) cannabinoid CB1 (CB1R), are pivotal importance control neuronal excitability. Facilitatory inhibitory functional interactions between A2AR CB1R have been reported,...
Cognitive dysfunction is an early clinical hallmark of Huntington's disease (HD) preceding the appearance motor symptoms by several years. Neuronal and altered corticostriatal connectivity have been postulated to be fundamental explain these disturbances. However, no treatments attenuate cognitive changes successful: reason may rely on idea that temporal sequence pathological as critical per se when new therapies are in development. To this aim, it becomes use HD mouse models which...
Olfactory impairment is a recognized early indicator of neurodegenerative diseases (NDs), such as Alzheimer's disease (AD). Intracellular aggregates hyperphosphorylated tau protein, referred to neurofibrillary tangles (NFTs), are hallmark AD. NFTs found in the olfactory bulb (OB) and entorhinal cortex (EC), both crucial for processing information. We explored hypothesis that typical lesions could appear progress along regions reach connected areas critically affected AD (e.g. EC hippocampal...
The function of the amyloid precursor protein (APP) is not fully understood, but its cleavage product beta (Aβ) together with neurofibrillary tangles constitute hallmarks Alzheimer's disease (AD). Yet, imbalance excitatory and inhibitory neurotransmission accompanied by loss synaptic functions, has been reported much earlier independent any detectable pathological markers. Recently, soluble APP fragments have shown to bind presynaptic GABA
Amyloid precursor protein (APP) cleavage by the β-secretase produces C99 transmembrane (TM) protein, which contains three dimerization-inducing Gly-x-x-x-Gly motifs. We demonstrate that dimeric TM orientations regulate precise lines γ-secretase. Of all possible imposed a coiled-coil to domain, dimer containing 33Gly-x-x-x-Gly37 motif in interface promoted Aβ42 processing line and APP intracellular domain-dependent gene transcription, including induction of BACE1 mRNA, enhancing amyloidogenic...
A key hallmark of Alzheimer's disease is the extracellular deposition amyloid plaques composed primarily amyloidogenic amyloid-β (Aβ) peptide. The Aβ peptide a product sequential cleavage Amyloid Precursor Protein, first step which gives rise to C-terminal Fragment (C99). Cleavage C99 by γ-secretase activity releases several lengths and Aβ42 isoform in particular has been identified as being neurotoxic. misfolding leads subsequent fibril formation nucleated polymerisation. This requires an...
Presenilin 1 (PS1) and 2 (PS2) are predominantly known as the catalytic subunits of γ-secretase complex that generates amyloid-β (Aβ) peptide, major constituent senile plaques found in brain Alzheimer's disease (AD) patients. Apart from their role activity, a growing number cellular functions have been recently attributed to PSs. Notably, PSs were be enriched mitochondria-associated membranes (MAMs) where mitochondria endoplasmic reticulum (ER) interact. PS2 was more specifically reported...
Abstract The β-amyloid peptide (Aβ) is found as amyloid fibrils in senile plaques, a typical hallmark of Alzheimer’s disease (AD). However, intermediate soluble oligomers Aβ are now recognized initiators the pathogenic cascade leading to AD. Studies using recombinant have shown that hexameric particular acts critical nucleus for self-assembly. We recently isolated assemblies from cellular model, and demonstrated their ability enhance aggregation vitro. Here, we report presence similar...
Abstract INTRODUCTION Amyloid-β (Aβ) and tau are brain hallmarks of Alzheimer’s disease (AD) also present in blood as soluble biomarkers or encapsulated extracellular vesicles (EVs). Our goal was to assess how plasma AD pathology correlate with number content EVs. METHODS Single-molecule enzyme-linked assays were used quantify Aβ42/40 samples neurally-derived EVs (NDEVs) from a cohort APOE ε4– ε4+ cognitively normal individuals (CN) patients. RESULTS Soluble ratio is decreased patients...
Abstract Background Amyloid-β (Aβ) and tau are brain hallmarks of Alzheimer’s disease (AD), also present in blood as soluble biomarkers or encapsulated extracellular vesicles (EVs). Our goal was to assess how plasma AD pathology correlate with the number content EVs. Methods Single-molecule enzyme-linked assays were used quantify Aβ42/40 samples neurally-derived EVs (NDEVs) from a cohort APOE ε4– ( n = 168) ε4+ 68) cognitively normal individuals patients 55). The ratio CD56 (Neuronal...
Most neurodegenerative diseases have the characteristics of proteinopathies, i.e. they cause lesions to appear in vulnerable regions nervous system, corresponding protein aggregates that progressively spread through neuronal network as symptoms progress. Alzheimer's disease is one these proteinopathies. It characterized by two lesions, neurofibrillary tangles (NFTs) and senile plaques, formed essentially amyloid peptides (Aβ). A combination factors ranging from genetic mutations...
Abstract A key hallmark of Alzheimer’s disease (AD) is the extracellular deposition amyloid plaques composed primarily amyloidogenic amyloid-β (Aβ) peptide. The Aβ peptide a product sequential cleavage Amyloid Precursor Protein (APP), first step which gives rise to C-terminal Fragment (C99). Cleavage C99 by γ-secretase activity releases several lengths and Aβ42 isoform in particular has been identified as being neurotoxic. misfolding leads subsequent fibril formation nucleated...
Abstract Presenilins 1 and 2 (PS1 PS2) are predominantly known as the catalytic subunits of γ-secretase complex which generates amyloid-β (Aβ) peptide, major constituent senile plaques found in brain Alzheimer’s disease (AD) patients. Apart from their role activity, a growing number cellular functions have been recently attributed to PSs. They involved synaptic transmission, endo-lysosomal function calcium homeostasis. PSs were also be enriched mitochondria-associated membranes (MAMs) where...
<h3></h3> Huntington9s disease (HD) patients and mouse models show learning memory impairment before the onset of motor symptoms. These cognitive impairments are thought to be caused by altered synaptic plasticity dendritic spine deficits. However molecular mechanisms underlying these changes still poorly understood. Among several factors it is well known that BDNF its receptors, TrkB p75NTR play a crucial role in plasticity. In this study we aim elucidate whether participates reduced...
Abstract Background The β-amyloid peptide (Aβ) plays a key role in Alzheimer’s disease. After its production by catabolism of the amyloid precursor protein (APP) through action presenilin 1 (PS1)- or 2 (PS2)-dependent γ-secretases, monomeric Aβ can assemble oligomers. In pathological context, this eventually leads to formation fibrils, which deposit senile plaques. Many studies suggest that toxicity is related soluble oligomeric intermediates. Among these, our interest focuses on hexameric...
Amyloid precursor protein (APP) cleavage by the β secretase produces C99 transmembrane (TM) protein, which contains three dimerization-inducing Gly-x-x-x-Gly motifs. We demonstrate that dimeric TM orientations regulate precise lines γ-secretase. Of all possible imposed a coiled coil to TM-cytosolic domain, dimer containing 33Gly-x-x-x-Gly37 motif in interface promoted Aβ42 processing line and AICD (APP Intracellular Domain)-dependent gene transcription, including induction of BACE1 mRNA,...
Abstract A key hallmark of Alzheimer’s disease (AD) is the extracellular deposition amyloid plaques composed primarily amyloidogenic amyloid-β (Aβ) peptide. The Aβ peptide a product sequential cleavage Amyloid Precursor Protein (APP), first step which gives rise to C-terminal Fragment (C99). Cleavage C99 by γ-secretase activity releases several lengths and Aβ42 isoform in particular has been identified as being neurotoxic. misfolding leads subsequent fibril formation nucleated...
Abstract Aging is a well-known risk factor for Alzheimer’s disease (AD) and other neurodegenerative pathologies, but the molecular cellular changes occurring in aging brain are poorly understood. AD pathology seems to correlate with appearance of cells that become senescent due progressive accumulation insults causing DNA damage. In this study, we investigated role senescence on by crossing an amyloid-β (Aβ) mouse model (5xFAD) genetically deficient RNA component telomerase (Terc -/- ). Our...
Abstract BackgroundThe β-amyloid peptide (Aβ) plays a key role in Alzheimer’s disease. After its production by catabolism of the amyloid precursor protein (APP) through action presenilin 1 (PS1)- or 2 (PS2)-dependent γ-secretases, monomeric Aβ can assemble oligomers. In pathological context, this eventually leads to formation fibrils, which deposit senile plaques. Many studies suggest that toxicity is related soluble oligomeric intermediates. Among these, our interest focuses on hexameric...
Abstract The β-amyloid peptide (Aβ) is the main constituent of senile plaques, a typical hallmark Alzheimer’s disease (AD). Monomeric Aβ generated through sequential processing amyloid precursor protein (APP), with final step involving γ-secretase activity. In AD, monomers assemble in oligomers and ultimately fibrils depositing plaques. Importantly, toxicity appears related to its soluble oligomeric intermediates. particular, recombinant studies described hexamers as critical nuclei. We...