Sergio Ferreira

Sergio Ferreira
Federal University of Rio de Janeiro | UFRJ · Instituto de Biofísica Carlos Chagas Filho (IBCCF)

PhD

About

262
Publications
33,523
Reads
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13,657
Citations
Additional affiliations
April 2009 - August 2009
University of Illinois, Urbana-Champaign
Position
  • Visiting Assistant Research Physicist
April 2007 - December 2007
University of Illinois, Urbana-Champaign
Position
  • Visiting Assistant Research Physicist
April 2005 - December 2007
Northwestern University
Position
  • Researcher

Publications

Publications (262)
Article
Full-text available
Physical exercise stimulates neuroprotective pathways, has pro-cognitive actions, and alleviates memory impairment in Alzheimer’s disease (AD). Irisin is an exercise-linked hormone produced by cleavage of fibronectin type III domain containing protein 5 (FNDC5) in skeletal muscle, brain and other tissues. Irisin was recently shown to mediate the br...
Article
Full-text available
Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC) countries remains a serious barrier. Here, we reported a survey to explore the ongoing work, needs, interests, potential barriers, and opportunities for future studies related to biomarkers. The results show that neuroimaging is the most used biomarker (73%), followed by...
Preprint
Alteration in the buffering capacity of the proteostasis network is an emerging feature of Alzheimer’s disease (AD), highlighting the occurrence of endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) is the main adaptive pathway to cope with protein folding stress at the ER. Inositol requiring enzyme-1 (IRE1) is an ER-located kin...
Preprint
Brain accumulation of soluble oligomers of the amyloid-β peptide (AβOs) has been implicated in synapse failure and memory impairment in Alzheimer's disease. Here, we show that treatment with NUsc1, a single-chain variable fragment antibody (scFv) that selectively targets AβOs, prevents the inhibition of long-term potentiation in hippocampal slices...
Article
Acute neurological alterations have been associated with SARS-CoV-2 infection. Additionally, it is becoming clear that coronavirus disease 2019 (COVID-19) survivors may experience long-term neurological abnormalities, including cognitive deficits and mood alterations. The mechanisms underlying acute and long-term impacts of COVID-19 in the brain ar...
Article
The discovery of insulin in 1921 revolutionized the treatment of diabetes and paved the way for numerous studies on hormone signalling networks and actions in peripheral tissues and in the central nervous system. Impaired insulin signalling, a hallmark of diabetes, is now established as a key component of Alzheimer disease (AD) pathology. Here, we...
Conference Paper
Full-text available
Background: Familial hypercholesterolemia (FH) is a genetic disorder caused by low-density lipoprotein receptor (LDLr) dysfunction, resulting in elevated plasma cholesterol levels. Previous reports have shown an interplay between LDLr and amyloid-β (Aβ) metabolism, a peptide linked to Alzheimer's disease. Indeed, LDLr-/- mice are more vulnerable t...
Preprint
Age increases the risk for cognitive impairment and is the single major risk factor for Alzheimer's disease (AD), the most prevalent form of dementia in the elderly. The pathophysiological processes triggered by aging that render the brain vulnerable to dementia involve, at least in part, changes in inflammatory mediators. Here we show that lipoxin...
Article
Full-text available
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Article
Background: Alzheimer's disease (AD) is the most common cause of dementia in the elderly and is characterized by progressive cognitive decline. Considerable evidence supports an important role of amyloid-β oligomers (AβOs) in the pathogenesis of AD, including the induction of aberrant glial activation and memory impairment. Objective: We have in...
Article
Background: Alzheimer's disease (AD) and Lewy body disease (LBD) are complex neurodegenerative disorders that have been associated with brain inflammation and impaired neurotransmission. Objective: We aimed to determine concentrations of multiple cytokines, chemokines, and neurotransmitters previously associated with brain inflammation and synap...
Article
Full-text available
Alzheimer’s disease (AD) is associated with memory impairment and altered peripheral metabolism. Mounting evidence indicates that abnormal signaling in a brain-periphery metabolic axis plays a role in AD pathophysiology. The activation of pro-inflammatory pathways in the brain, including the interleukin-6 (IL-6) pathway, comprises a potential point...
Article
Introduction: Dementia has been associated with COVID-19 prevalence, but whether this reflects higher infection, older age of patients, or disease severity remains unclear. Methods: We investigated a cohort of 12,863 UK Biobank community-dwelling individuals > 65 years old (1814 individuals ≥ 80 years old) tested for COVID-19. Individuals were s...
Article
Sepsis survivors show long-term impairments, including alterations in memory and executive function. Evidence suggests that systemic inflammation contributes to the progression of Alzheimeŕs disease (AD), but the mechanisms involved in this process are still unclear. Boosted (trained) and diminished (tolerant) innate immune memory has been describe...
Article
Amyloid-β (Aβ) dysmetabolism is thought to be the main trigger for neurodegenerative events in Alzheimer's disease (AD). In particular, soluble Aβ oligomers (AβOs) are proposed as key mediators of synaptic and cognitive dysfunction in AD. Over the past few decades, AβOs prepared from synthetic Aβ have been widely applied in in vitro and in vivo mod...
Article
Although the brain was once considered an insulin‐independent organ, insulin signalling is now recognised as being central to neuronal health and to the function of synapses and brain circuits. Defective brain insulin signalling, as well as related signalling by insulin‐like growth factor 1 (IGF‐1), is associated with neurological disorders, includ...
Article
Full-text available
Across Latin American and Caribbean countries (LACs), the fight against dementia faces pressing challenges, such as heterogeneity, diversity, political instability, and socioeconomic disparities. These can be addressed more effectively in a collaborative setting that fosters open exchange of knowledge. In this work, the Latin American and Caribbean...
Article
Full-text available
Background The lack of effective treatments for Alzheimer’s disease (AD) reflects an incomplete understanding of disease mechanisms. Alterations in proteins involved in mitochondrial dynamics, an essential process for mitochondrial integrity and function, have been reported in AD brains. Impaired mitochondrial dynamics causes mitochondrial dysfunct...
Article
Neuronal protein synthesis is essential for long-term memory consolidation, and its dysregulation is implicated in various neurodegenerative disorders, including Alzheimer's disease (AD). Cellular stress triggers the activation of protein kinases that converge on the phosphorylation of eukaryotic translation initiation factor 2a (eIF2a), which atte...
Article
Alzheimer's disease (AD) is the main cause of dementia in the elderly and is characterized by abnormal accumulation of the beta‐amyloid peptide (Aß) in the brain. Considerable evidence has shown that soluble Abeta oligomers (AßOs) are the main neurotoxins involved in synaptic dysfunction and the memory loss. We evaluated the therapeutic potential o...
Preprint
Full-text available
Neuronal protein synthesis is essential for long-term memory consolidation. Conversely, dysregulation of protein synthesis has been implicated in a number of neurodegenerative disorders, including Alzheimer’s disease (AD). Several types of cellular stress trigger the activation of protein kinases that converge on the phosphorylation of eukaryotic t...
Article
Converging evidence indicates that neurotoxicity and memory impairment in Alzheimer's disease is induced by brain accumulation of soluble amyloid-β oligomers (AβOs). Physiological metals are poorly distributed and concentrated in the senile plaques typical of Alzheimer's disease, where they may be coordinated to the amyloid-β peptide (Aβ). Indeed,...
Article
Systemic multimorbidity is highly prevalent in the elderly and, remarkably, coexisting neuropathological markers of Alzheimer's (AD) and cerebrovascular (CVD) diseases are found at autopsy in most brains of patients clinically diagnosed as AD. Little is known on neurodegeneration peculiar to comorbidities, especially at early stages when pathogenes...
Article
Full-text available
Introduction: Irisin is a novel hormone originally identified for its role as a regulator of peripheral metabolism and recently found to protect synapses and rescue memory in mouse models of Alzheimer's disease (AD). However, whether and how cerebrospinal fluid (CSF) irisin varies in relation to canonical AD biomarkers and cognition in humans rema...
Article
Full-text available
Amyloid‐β (Aβ) dysmetabolism is tightly associated with pathological processes in Alzheimer’s disease (AD). Currently, it is thought that, in addition to Aβ fibrils that give rise to plaque formation, Aβ aggregates into non‐fibrillar soluble oligomers (AβOs). Soluble AβOs have been extensively studied for their synaptotoxic and neurotoxic propertie...
Article
Full-text available
Modulation of brain activity is one of the main mechanisms capable of demonstrating the synchronization dynamics of neural oscillations. In epilepsy, modulation is a key concept since seizures essentially result from neural hypersynchronization and hyperexcitability. In this study, we have introduced a time-dependent index based on the Kullback-Lei...
Article
Emerging evidence indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), can cause neurological complications. We provide a brief overview of these recent observations and discuss some of their possible implications. In particular, given the global dimension of the cu...
Article
Full-text available
Alzheimer’s disease (AD) is the main cause of dementia in the elderly. Although activation of brain insulin signaling has been shown to be neuroprotective, to preserve memory in AD models, and appears beneficial in patients, the role of insulin-like growth factor 1 (IGF1) remains incompletely understood. We found reduced active/inactive IGF1 ratio...
Article
Full-text available
Obesity has been associated with cognitive decline, atrophy of brain regions related to learning and memory, and higher risk of developing dementia. However, the molecular mechanisms underlying these neurological alterations are still largely unknown. Here, we investigate the effects of palmitate, a saturated fatty acid present at high amounts in f...
Article
Full-text available
Familial hypercholesterolemia (FH) is a genetic disorder caused by dysfunction of low density lipoprotein receptors (LDLr), resulting in elevated plasma cholesterol levels. FH patients frequently exhibit cognitive impairment, a finding recapitulated in LDLr deficient mice (LDLr-/-), an animal model of FH. In addition, LDLr-/- mice are more vulnerab...
Article
Full-text available
Background: Mesenchymal stem cells (MSCs) have been explored as promising tools for treatment of several neurological and neurodegenerative diseases. MSCs release abundant extracellular vesicles (EVs) containing a variety of biomolecules, including mRNAs, miRNAs, and proteins. We hypothesized that EVs derived from human Wharton's jelly would act a...
Article
Full-text available
Neurological complications affecting the central nervous system have been reported in adult patients infected by Zika virus (ZIKV) but the underlying mechanisms remain unknown. Here, we report that ZIKV replicates in human and mouse adult brain tissue, targeting mature neurons. ZIKV preferentially targets memory-related brain regions, inhibits hipp...
Article
Full-text available
Harmful environmental stimuli during critical stages of development can profoundly affect behavior and susceptibility to diseases. Alzheimer disease (AD) is the most frequent neurodegenerative disease, and evidence suggest that inflammatory conditions act cumulatively, contributing to disease onset. Here we investigated whether infection early in l...
Article
Alzheimer's disease (AD) is a progressive and irreversible disorder whose pathological features include β‐amyloid (Aβ) plaques and neuronal and synaptic loss. Metals such as iron, copper, and zinc are increased in the brains of patients with AD. Those metals can interact with Aβ, resulting in the promotion of Aβ deposition and formation of plaque....
Article
Full-text available
Western societies experienced drastic changes in eating habits during the past century. The modern nutritional profile, typically rich in saturated fats and refined sugars, is recognized as a major contributing factor, along with reduced physical activity, to the current epidemics of metabolic disorders, notably obesity and diabetes. Alongside thes...
Article
Full-text available
Defective brain hormonal signaling has been associated with Alzheimer’s disease (AD), a disorder characterized by synapse and memory failure. Irisin is an exercise-induced myokine released on cleavage of the membrane-bound precursor protein fibronectin type III domain-containing protein 5 (FNDC5), also expressed in the hippocampus. Here we show tha...
Article
Full-text available
Converging evidence indicates that dysfunctions in glutamatergic neurotransmission and in the glutamate-glutamine cycle play a role in the pathophysiology of schizophrenia. Here, we investigated glutamate and glutamine levels in the blood of patients with recent onset schizophrenia or chronic schizophrenia compared to healthy controls. Compared wit...
Article
Full-text available
The current absence of effective treatments for Alzheimer’s disease (AD) and Parkinson’s disease (PD) reflects an incomplete knowledge of the underlying disease processes. Considerable efforts have been made to investigate the central pathological features of these diseases, giving rise to numerous attempts to develop compounds that interfere with...
Article
Full-text available
Recent evidence suggests that Alzheimer's disease (AD) and depression share common mechanisms of pathogenesis. In particular, deregulation of glutamate-mediated excitatory signaling may play a role in brain dysfunction in both AD and depression. We have investigated levels of glutamate and its precursor glutamine in the cerebrospinal fluid (CSF) of...
Article
Mania is characterized by elevated drive and mood but animal models of mania have often neglected elevated mood. Ultrasonic vocalizations (USV) of 50-kHz emitted by rats are thought to index the subject's positive affective state. Fifty-kHz USV emission is increased by amphetamine, an effect blocked by lithium administration. Sleep deprivation (SD)...
Data
Figure S1. PKA activation is required for GLP‐1 receptor‐mediated prevention of AβO‐induced synapse loss. (A) Representative images of cultured hippocampal neurons exposed to 500 nm AβOs (or vehicle) for 3 h and immunolabeled for synaptophysin (green)/PSD‐95 (red). Where indicated, neurons were pre‐incubated with liraglutide (300 nm) or H‐89 (10 μm...
Data
Figure S2. Intracerebroventricular AβO injection or liraglutide treatment does not interfere with hippocampal insulin levels in mice. Hippocampal insulin levels were measured 9 days after i.c.v. injection of AβOs (10 pmol) or vehicle. Prior to AβO injection, animals were pretreated for 7 days with saline or liraglutide (25 nmol/kg; i.p.; n = 5–6 an...
Data
Figure S3. Effects of liraglutide on AβO‐induced loss of insulin receptor in the frontal cortex, hippocampus, and amygdala of NHPs. Representative images of frontal cortex, hippocampus, and amygdala of sham‐operated, AβO‐injected or liraglutide‐treated AβO‐injected NHPs (as indicated) immunolabeled for IRα (A, E, I) or IRβ (C, G, K). Scale bar = 50...
Data
Figure S5. Representative images of synapse densities in the frontal cortex and amygdala of NHPs. Representative images from the frontal cortex or amygdala of sham‐operated, AβO‐injected or liraglutide‐treated AβO‐injected NHPs immunolabeled for synaptophysin (green) (A, C) and PSD‐95 (B, D) (red). Merged images from amygdala areas shown in E. Scal...
Data
Figure S4. Liragutide attenuates AβO‐induced synapse damage in the hippocampus and amygdala of NHPs. Representative images from the dentate gyrus of sham‐operated, AβO‐injected or liraglutide‐treated AβO‐injected NHPs (as indicated) immunolabeled for synaptophysin (A) or PSD‐95 (D). Merged images are shown in (G). Nuclear staining (DAPI) is shown i...
Data
Figure S6. Representative images of hippocampus and amygdala immunolabeled for AT100 or CP13 in the NHPs. Representative images of dentate gyrus and amygdala of sham‐operated, AβO‐injected or liraglutide‐treated AβO‐injected NHPs (as indicated) immunolabeled for AT100 (A) or CP13 (B). Scale bar = 50 μm in A and 20 μm in B. For CP13, z‐stack project...
Data
Table S3. Nomenclature for specific brain regions analyzed following intracerebroventricular injections of AβOs in NHPs
Article
Background: Slice cultures have been prepared from several organs. With respect to the brain, advantages of slice cultures over dissociated cell cultures include maintenance of the cytoarchitecture and neuronal connectivity. Slice cultures from adult human brain have been reported and constitute a promising method to study neurological diseases. D...
Article
Alzheimer's disease (AD) is the main form of dementia in the elderly and affects greater than 47 million people worldwide. Care for AD patients poses very significant personal and economic demands on individuals and society, and the situation is expected to get even more dramatic in the coming decades unless effective treatments are found to halt t...
Article
Full-text available
Alzheimer's disease (AD) is a devastating neurological disorder that still lacks an effective treatment, and this has stimulated an intense pursuit of disease-modifying therapeutics. Given the increasingly recognized link between AD and defective brain insulin signaling, we investigated the actions of liraglutide, a glucagon-like peptide-1 (GLP-1)...
Article
Full-text available
Sepsis survivors frequently develop late cognitive impairment. Because little is known on the mechanisms of post-septic memory deficits, there are no current effective approaches to prevent or treat such symptoms. Here, we subjected mice to severe sepsis induced by cecal ligation and puncture (CLP) and evaluated the sepsis-surviving animals in the...