A5031545850- Alzheimer's disease research and treatments
- Tryptophan and brain disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Neuroscience and Neuropharmacology Research
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
- Genetics and Neurodevelopmental Disorders
- Adipose Tissue and Metabolism
- Nuclear Receptors and Signaling
- Fatty Acid Research and Health
- Stress Responses and Cortisol
- Regulation of Appetite and Obesity
- Computational Drug Discovery Methods
- Cholesterol and Lipid Metabolism
- Protein Degradation and Inhibitors
- Peroxisome Proliferator-Activated Receptors
- Cerebrovascular and genetic disorders
- Neurological Disorders and Treatments
- Neurogenetic and Muscular Disorders Research
- Nerve injury and regeneration
- Inflammasome and immune disorders
- Diet and metabolism studies
- Advanced Glycation End Products research
- Metabolomics and Mass Spectrometry Studies
Universidade Federal do Rio de Janeiro
2012-2024
Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
2017-2018
Institute of Biochemistry
2016
Abstract Alzheimer's disease ( AD ) is associated with peripheral metabolic disorders. Clinical/epidemiological data indicate increased risk of diabetes in patients. Here, we show that intracerebroventricular infusion ‐associated Aβ oligomers (AβOs) mice triggered glucose intolerance, a phenomenon further verified two transgenic mouse models . Systemically injected AβOs failed to induce suggesting target brain regions involved control. Accordingly, affected hypothalamic neurons culture,...
Brain accumulation of soluble amyloid-β oligomers (AβOs) has been implicated in synapse failure and cognitive impairment Alzheimer's disease (AD). However, whether how different sizes induce dysfunction is a matter controversy. Here, we report that low-molecular-weight (LMW) high-molecular-weight (HMW) Aβ differentially impact synapses memory. A single intracerebroventricular injection LMW AβOs (10 pmol) induced rapid persistent mice. On the other hand, memory deficit by HMW was found to be...
Considerable clinical and epidemiological evidence links Alzheimer's disease (AD) depression. However, the molecular mechanisms underlying this connection are largely unknown. We reported recently that soluble Aβ oligomers (AβOs), toxins accumulate in AD brains thought to instigate synapse damage memory loss, induce depressive-like behavior mice. Here, we report mechanism action involves AβO-induced microglial activation, aberrant TNF-α signaling, decreased brain serotonin levels....
Alteration in the buffering capacity of proteostasis network is an emerging feature Alzheimer's disease (AD), highlighting occurrence endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) main adaptive pathway to cope with folding stress at ER. Inositol-requiring enzyme-1 (IRE1) operates as a central ER sensor, enabling establishment and repair programs through control expression transcription factor X-box binding 1 (XBP1). To artificially enforce UPR AD brain, we developed...
Introduction: Irisin is a novel hormone originally identified for its role as regulator of peripheral metabolism and recently found to protect synapses rescue memory in mouse models Alzheimer's disease (AD). However, whether how cerebrospinal fluid (CSF) irisin varies relation canonical AD biomarkers cognition humans remains unknown. Methods: We determined CSF levels brain-derived neurotrophic factor (BDNF) examined their correlations with amyloid beta (Aβ)42, total tau, Mini-Mental State...
Abstract INTRODUCTION Impaired brain protein synthesis, synaptic plasticity, and memory are major hallmarks of Alzheimer's disease (AD). The ketamine metabolite ( 2R,6R )‐hydroxynorketamine (HNK) has been shown to modulate but its effects on in AD models remain elusive. METHODS We investigated the HNK hippocampal long‐term potentiation (LTP), mouse models. RESULTS activated extracellular signal‐regulated kinase 1/2 (ERK1/2), mechanistic target rapamycin (mTOR), p70S6 1 (S6K1)/ribosomal S6...
Alzheimer's disease (AD) and Lewy body (LBD) are complex neurodegenerative disorders that have been associated with brain inflammation impaired neurotransmission.We aimed to determine concentrations of multiple cytokines, chemokines, neurotransmitters previously synapse function in cerebrospinal fluid (CSF) from AD LBD patients.We examined a panel 50 analytes comprising neurotransmitters, hormones CSF cohort patients diagnosed mild cognitive impairment (MCI), AD, LBD, or non-demented...
Abstract The proteasome plays key roles in synaptic plasticity and memory by regulating protein turnover, quality control, elimination of oxidized/misfolded proteins. Here, we investigate function localization at synapses Alzheimer’s disease (AD) post-mortem brain tissue experimental models. We found a marked increase ubiquitinylated proteins AD hippocampi compared to controls. Using several models, show that amyloid-β oligomers (AβOs) inhibit activity trigger reduction content. further...
Abstract Introduction Depression is frequent among older adults and a risk factor for dementia. Identifying molecular links between depression dementia necessary to shed light on shared disease mechanisms. Reduced brain‐derived neurotrophic (BDNF) neuroinflammation are implicated in the pathophysiology of The exercise‐induced hormone, irisin, increases BDNF improves cognition animal models Alzheimer's disease. Lipoxin A4 lipid mediator with anti‐inflammatory activity. However, roles irisin...
Age increases the risk for cognitive impairment and is single major factor Alzheimer's disease (AD), most prevalent form of dementia in elderly. The pathophysiological processes triggered by aging that render brain vulnerable to involve, at least part, changes inflammatory mediators. Here we show lipoxin A4 (LXA4), a lipid mediator inflammation resolution known stimulate endocannabinoid signaling brain, reduced central nervous system. We demonstrate genetic suppression 5-lipoxygenase...
Abstract Alzheimer’s disease (AD) is characterized by progressive memory decline. Converging evidence indicates that hippocampal mRNA translation (protein synthesis) defective in AD. Here, we show genetic reduction of the translational repressors, Fragile X messenger ribonucleoprotein (FMRP) or eukaryotic initiation factor 4E (eIF4E)-binding protein 2 (4E-BP2), prevented attenuation synthesis and impairment induced AD-linked amyloid-β oligomers (AβOs) mice. Moreover, 4E-BP2 rescued deficits...
Abstract Background Alzheimer’s disease (AD) stands as the predominant form of dementia worldwide. The pathogenesis AD encompasses elevated brain levels amyloid‐β oligomers (AβOs), recognized central neurotoxins linked to AD. accumulation AβOs is neurotoxic, resulting in detrimental effects such synapse loss, mitochondrial dysfunction, and impairment proteostasis mechanisms. Neuroinflammation, particularly activation microglia astrocytes pro‐inflammatory states, has been implicated various...
Abstract Background Alzheimer’s disease (AD) is a progressive neurodegenerative characterized by synapse and memory failure, severe cognitive impairment. Physical exercise stimulates neuroprotective pathways, has pro‐cognitive actions, been reported to alleviate impairment in AD. Irisin, an exercise‐induced hormone, secreted following proteolytic cleavage of fibronectin type‐III‐domain‐containing 5 (FNDC5). Irisin regulates peripheral metabolism, found protect synapses rescue mouse models...
Abstract Background The proteasome plays key roles in synaptic plasticity and memory by regulating protein turnover, quality control, elimination of oxidized/misfolded proteins. Here, we investigate function localization at synapses Alzheimer’s disease (AD) post‐mortem brain tissue experimental models. Method We used primary hippocampal cultures, amyloid‐β oligomers (AβO)‐injected or transgenic animal models, human to determine subcellular localization. further induced inhibition vitro vivo...
Abstract Alteration in the buffering capacity of proteostasis network is an emerging feature Alzheimer’s disease (AD), highlighting occurrence endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) main adaptive pathway to cope with folding stress at ER. Inositol requiring enzyme-1 (IRE1) ER-located kinase and endoribonuclease that operates as a central ER sensor, enabling establishment repair programs through control expression transcription factor X-Box binding 1 (XBP1). A...
Alzheimer’s disease (AD) is associated with peripheral metabolic disorders. Clinical/epidemiological data indicate increased risk of diabetes in AD patients. Here, we show that intracerebroventricular infusion AD-associated Ab oligomers (AbOs) mice triggered glucose intolerance, a phenomenon further verified two transgenic mouse models AD. Systemically injected AbOs failed to induce suggesting target brain regions involved control. Accordingly, affected hypothalamic neurons culture, inducing...