Fabio Di Domenico

Fabio Di Domenico
Sapienza University of Rome | la sapienza · Department of Biochemical Sciences "Alessandro Rossi Fanelli

Ph.D in Biochemistry

About

163
Publications
68,743
Reads
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11,173
Citations
Citations since 2017
69 Research Items
8911 Citations
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201720182019202020212022202305001,0001,500
201720182019202020212022202305001,0001,500
Additional affiliations
December 2010 - November 2015
Sapienza University of Rome
Position
  • Researcher
January 2010 - present
Sapienza University of Rome
Position
  • Research Assistant
May 2009 - July 2010
University of Kentucky
Position
  • PostDoc Position

Publications

Publications (163)
Article
Metformin is the most common anti-diabetic drug and a promising therapy for disorders beyond diabetes, including Rett syndrome (RTT), a rare neurologic disease characterized by severe intellectual disability. A 10-day-long treatment rescued aberrant mitochondrial activity and restrained oxidative stress in a female RTT mouse model. However, this tr...
Chapter
Protein homeostasis or “proteostasis” represent the process that regulates the balance of the intracellular functional and “healthy” proteins. Proteostasis is fundamental to preserve physiological metabolic processes in the cell and it allow to respond to any given stimulus as the expression of components of the proteostasis network is customized a...
Article
The cells possess several mechanisms to counteract the over-production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), including enzymes such as superoxide dismutase, catalase and glutathione peroxidase. Moreover, an important sensor involved in the anti-oxidant response is KEAP1-NRF2-ARE signaling complex. Under oxidative str...
Chapter
The complexity of Down Syndrome (DS) neurodegeneration involves multiple molecular mechanisms, similar to what observed in Alzheimer's disease (AD) brain, including the deposition of beta-amyloid (Aβ) into senile plaques and tau hyperphosphorylation in neurofibrillary tangles. Intriguingly, several trisomic genes in addition to being primarily link...
Article
Full-text available
Introduction: Intellectual disability, accelerated aging, and early-onset Alzheimer-like neurodegeneration are key brain pathological features of Down syndrome (DS). Although growing research aims at the identification of molecular pathways underlying the aging trajectory of DS population, data on infants and adolescents with DS are missing. Meth...
Article
Alzheimer's disease (AD) is the most common form of dementia in the elderly followed by vascular dementia. In addition to clinically diagnosed dementia, cognitive dysfunction has been reported in diabetic patients. Recent studies are now beginning to recognize type 2 diabetes mellitus (T2DM), characterized by chronic hyperglycemia and insulin resis...
Article
Full-text available
The disturbance of protein O-GlcNAcylation is emerging as a possible link between altered brain metabolism and the progression of neurodegeneration. As observed in brains with Alzheimer’s disease (AD), flaws of the cerebral glucose uptake translate into reduced protein O-GlcNAcylation, which promote the formation of pathological hallmarks. A high-f...
Article
Alzheimer’s disease (AD) is the most prevalent form of dementia in the elderly population and has worldwide impact. The etiology of the disease is complex and results from the confluence of multiple mechanisms ultimately leading to neuronal loss and cognitive decline. Among risk factors, aging is the most relevant and accounts for several pathogeni...
Article
Full-text available
Down syndrome (DS) is the most common genomic disorder characterized by the increased incidence of developing early Alzheimer’s disease (AD). In DS, the triplication of genes on chromosome 21 is intimately associated with the increase of AD pathological hallmarks and with the development of brain redox imbalance and aberrant proteostasis. Increasin...
Article
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Preprint
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Article
Dysregulation of brain insulin signaling with reduced downstream neuronal survival and plasticity mechanisms are fundamental abnormalities observed in Alzheimer disease (AD). This phenomenon, known as brain insulin resistance, is associated with poor cognitive performance and is driven by the inhibition of IRS1. Since Down syndrome (DS) and AD neur...
Article
Full-text available
Tauopathies are a group of more than twenty known disorders that involve progressive neurodegeneration, cognitive decline and pathological tau accumulation. Current therapeutic strategies provide only limited, late-stage symptomatic treatment. This is partly due to lack of understanding of the molecular mechanisms linking tau and cellular dysfuncti...
Preprint
Full-text available
the PDF can be download freely on pubmed. https://pubmed.ncbi.nlm.nih.gov/33634751/
Cover Page
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Article
High fat diet (HFD) is the most commonly used experimental model of obesity and insulin resistance, resembling the hallmarks of humans metabolic syndromes. It causes detrimental effects on brain function, but the molecular mechanisms involved are still poorly understood. Recent studies show that HFD may lead to the reduction of glucose uptake, whic...
Article
Alterations of brain insulin signalling are a common pathophysiological mechanism leading to dementia in AD and Type 2‐Diabetes Mellitus (T2DM). These alterations are often associated with mitochondrial stress, failure of energy metabolism, synaptic loss and ultimately neurodegeneration. Studies from our group identified impairment of BVR‐A – a reg...
Article
Many neurodegenerative disorders in which aberrant protein conformers aggregate into pathological inclusions, such as tauopathies, also present endoplasmic reticulum stress and chronic activation of the PERK branch of the unfolded protein response (UPR). The adaptive effects of the PERK pathway include reduction of translation by transient inhibiti...
Article
Down syndrome (DS) is related with an increased incidence of Alzheimer’s disease (AD) neuropathology. Among the putative mechanisms leading neurodegeneration, the reduction of cerebral glucose metabolism may trigger brain damage by impacting the hexosamine biosynthetic pathway (HBP). As reported in AD, defective HBP is responsible for flawed protei...
Article
Full-text available
Down syndrome (DS) is the most common chromosomal disorder and the leading genetic cause of intellectual disability in humans, which results from the triplication of chromosome 21. To search for biomarkers for the early detection and exploration of the disease mechanisms, here, we investigated the protein expression signature of peripheral blood mo...
Article
Full-text available
Protein O-GlcNAcylation is a nutrient-related post-translational modification that, since its discovery some 30 years ago, has been associated with the development of neurodegenerative diseases. As reported in Alzheimer’s disease (AD), flaws in the cerebral glucose uptake translate into reduced hexosamine biosynthetic pathway flux and subsequently...
Preprint
Full-text available
Tauopathies are a group of more than twenty known disorders that involve progressive neurodegeneration, cognitive decline, and pathological tau accumulation. Current therapeutic strategies provide only limited, late-stage symptomatic treatment. This is partly due to lack of understanding of the molecular mechanisms linking tau and cellular dysfunct...
Article
A major challenge in neurobiology is the identification of the mechanisms by which protein misfolding leads to cellular toxicity. Many neurodegenerative disorders, in which aberrant protein conformers aggregate into pathological inclusions, present the chronic activation of the PERK branch of the unfolded protein response. The adaptive effects of t...
Article
Full-text available
Biliverdin reductase-A (BVR-A) impairment is associated with increased accumulation of oxidatively-damaged proteins along with the impairment of autophagy in the brain during neurodegenerative disorders. Reduced autophagy inhibits the clearance of misfolded proteins, which then form neurotoxic aggregates promoting neuronal death. The aim of our stu...
Article
Full-text available
Compelling evidence supports the role of oxidative stress in Alzheimer’s disease (AD) pathophysiology. Interestingly, Herpes simplex virus-1 (HSV-1), a neurotropic virus that establishes a lifelong latent infection in the trigeminal ganglion followed by periodic reactivations, has been reportedly linked both to AD and to oxidative stress conditions...
Article
Full-text available
Metformin is the first-line therapy for diabetes, even in children, and a promising attractive candidate for drug repurposing. Mitochondria are emerging as crucial targets of metformin action both in the periphery and in the brain. The present study evaluated whether treatment with metformin may rescue brain mitochondrial alterations and contrast t...
Article
Dysregulation of insulin signaling pathway with reduced downstream neuronal survival and plasticity mechanisms is a fundamental abnormality observed in Alzheimer's disease (AD) brain. This phenomenon, known as brain insulin resistance, is associated with poor cognitive performance and is driven by the uncoupling of insulin receptor (IR) from its di...
Article
Full-text available
The ultraviolet (UV) component of solar radiation is the major driving force of skin carcinogenesis. Most of studies on UV carcinogenesis actually focus on DNA damage while their proteome-damaging ability and its contribution to skin carcinogenesis have remained largely underexplored. A redox proteomic analysis of oxidized proteins in solar-induced...
Article
Introduction: Autophagy is one of the most conserved clearance systems through which eukaryotes manage to handle dysfunctional and excess organelles and macromolecules. This catabolic process has not only a role in the maintenance of basal turnover of cellular components, but it is also essential in cells adaptation to stress conditions. In the las...
Article
A decline in mitochondrial function plays a key role in the aging process and increases the incidence of age-related disorders, including Alzheimer disease (AD). Mitochondria—the power station of the organism—can affect several different cellular activities, including abnormal cellular energy generation, response to toxic insults, regulation of met...
Article
Full-text available
Impairment of biliverdin reductase-A (BVR-A) is an early event leading to brain insulin resistance in AD. Intranasal insulin (INI) administration is under evaluation as a strategy to alleviate brain insulin resistance; however, the molecular mechanisms underlying INI beneficial effects are still unclear. We show that INI improves insulin signalling...
Article
Full-text available
Increasing evidences support the notion that the impairment of intracellular degradative machinery is responsible for the accumulation of oxidized/misfolded proteins that ultimately results in the deposition of protein aggregates. These events are key pathological aspects of “protein misfolding diseases” including Alzheimer disease (AD). Interestin...
Article
Hyper-active GSK-3β favors Tau phosphorylation during the progression of Alzheimer's disease (AD). Akt is one of the main kinases inhibiting GSK-3β and its activation occurs in response to neurotoxic stimuli including, i.e., oxidative stress. Biliverdin reductase-A (BVR-A) is a scaffold protein favoring the Akt-mediated inhibition of GSK-3β. Reduce...
Article
Biliverdin reductase-A (BVR-A) is a serine/threonine/tyrosine kinase involved in the regulation of insulin signaling. In vitro studies have demonstrated that BVR-A is a substrate of the insulin receptor and regulates IRS1 by avoiding its aberrant activation, and in animal model of obesity the loss of hepatic BVR-A has been associated with glucose/i...
Article
Full-text available
Background: Down syndrome (DS) individuals, by the age of 40s, are at increased risk to develop Alzheimer-like dementia, with deposition in brain of senile plaques and neurofibrillary tangles. Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain, prior and after the development of Alzheimer Disease (AD). The aberr...
Article
Alzheimer's disease (AD) is a progressive form of dementia characterized by increased production of amyloid-β plaques and hyperphosphorylated tau protein, mitochondrial dysfunction, elevated oxidative stress, reduced protein clearance, among other. Several studies showed systemic modifications of immune and inflammatory systems due, in part, to dec...
Article
Brain insulin resistance is associated with an increased Aβ production in AD although the molecular mechanisms underlying this link are still largely unknown. Biliverdin reductase-A (BVR-A) is a unique Ser/Thr/Tyr kinase regulating insulin signalling. Studies from our group, demonstrated that BVR-A impairment is among the earliest events favoring b...
Article
Alzheimer disease (AD) is a neurodegenerative disorder characterized by progressive loss of memory, reasoning and other cognitive functions. Pathologically, patients with AD are characterized by deposition of senile plaques (SPs), formed by β-amyloid (Aβ), and neurofibrillary tangles (NTFs) that consist of aggregated hyperphosphorylated tau protein...
Article
PET scan analysis demonstrated the early reduction of cerebral glucose metabolism in Alzheimer disease (AD) patients that can make neurons vulnerable to damage via the alteration of the hexosamine biosynthetic pathway (HBP). Defective HBP leads to flawed protein O-GlcNAcylation coupled, by a mutual inverse relationship, with increased protein phosp...
Article
Full-text available
Down Syndrome (DS) individuals by the age of 40s are at increased risk to develop Alzheimer's dementia (AD), with deposition of senile plaques and neurofibrillary tangles. Aberrant mTOR signaling in the brain affects multiple pathways including energy metabolism, mitochondrial function, oxidative stress and autophagy, that are key players in age-re...
Article
Alzheimer's disease (AD) is a progressive form of dementia characterized by increased production of amyloid-β plaques and hyperphosphorylated tau protein, mitochondrial dysfunction, elevated oxidative stress (OS), reduced protein clearance among others. Several studies showed systemic modifications of immune and inflammatory systems due, in part, t...
Article
Down syndrome (DS) is the most common chromosomal disorder and the leading genetic cause of intellectual disability in humans, which results from the triplication of chromosome 21. DS individuals have an increased risk of developing Alzheimer's disease (AD)-like pathology and dementia by the age of 40 due to the triplication of several genes involv...
Article
Down syndrome (DS), the most frequent chromosomal abnormality in humans, results from complete or partial trisomy of chromosome 21 (Chr21). Though there is intellectual disability in DS people from birth, at about 40-50 years of age conversion to Alzheimer disease (AD)-like neuropathology and dementia often occurs. The mammalian target of rapamycin...
Article
The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase involved in the regulation of protein synthesis and degradation, longevity and cytoskeletal formation. The mTOR pathway represents a key growth and survival pathway involved in several diseases such as cancer, obesity, cardiovascular disease and neurodegenerative diseases...
Article
PET studies have demonstrated the early deficiency of cerebral glucose metabolism in AD patients. Reduced glucose utilization lead to altered protein O-GlcNAcylation, which might represent a link between glucose hypometabolism and the progression of AD. Increasing evidence support, in AD brain, a general decrease of protein O-GlcNAcylation coupled...
Article
Down Syndrome (DS) individuals by the age of 40ys develop a type of dementia that has the same characteristics as Alzheimer disease (AD). Previous studies in DS and AD brain suggest common neurodegenerative pathways including mitochondrial dysfunction, oxidative stress (OS) and reduced glucose metabolism. In addition, several studies suggest a link...
Article
Tauopathies, the most common of which is Alzheimer’s disease (AD), constitute the most crippling neurodegenerative threat to our aging population. Tauopathic patients have significant cognitive decline accompanied by irreversible and severe brain atrophy, and it is thought that neuronal dysfunction begins years before diagnosis. Our current underst...
Article
Introduction: The mTOR pathway is involved in the regulation of a wide repertoire of cellular functions in the brain and its dysregulation is emerging as a leitmotif in a large number of neurological disorders. In AD, altered mTOR signaling contributes to the inhibition of autophagy deposition of Aβ and tau aggregates and to the alteration of sever...
Article
Alzheimer disease (AD) is the most common form of dementia in the elderly population, characterized by a gradual deterioration of memory and other cognitive functions. The major pathological characteristics of AD brains are the presence of senile plaques, made of amyloid β-peptide (Aβ), neurofibrillary tangles, composed of hyperphosphorylated tau p...
Article
Brain insulin resistance (b.i.r.) was proposed as a mechanistic mediator of the cognitive deficits observed in Alzheimer disease (AD). Interestingly, the efficacy of intranasal insulin (I-Ins) administration – which allows to directly transport insulin to the CNS – was proposed as an innovative therapeutic strategy to alleviate cognitive dysfunctio...
Article
Alzheimer disease (AD), a multifactorial neurodegenerative disorder that represents one of the most disabling conditions in the aged population, shares many features in common with systemic insulin resistance diseases, including reduced insulin-stimulated growth and survival signaling, increased oxidative stress, pro-inflammatory cytokine activatio...
Article
Aims Among the putative mechanisms proposed to be common factors in Down Syndrome (DS) and Alzheimer disease (AD) neuropathology, deficits in protein quality control has emerged as a unifying mechanism of neurodegeneration. Considering that disturbance of protein degradative systems are present in DS and that oxidized/misfolded proteins require pol...
Article
Oxidative stress is involved in various and numerous pathological states including several age-related neurodegenerative diseases. Peroxidation of the membrane lipid bilayer is one of the major sources of free radical-mediated injury that directly damages neurons causing increased membrane rigidity, decreased activity of membrane-bound enzymes, imp...
Article
Significance: Alzheimer disease (AD), a multifactorial neurodegenerative disorder that represents the most disabling condition in the aged, shares many features of insulin resistance diseases, suggesting AD can be considered a metabolic disease, characterized by reduced insulin signaling, increased oxidative stress, pro-inflammatory cytokine activ...
Article
Aims: Among the putative mechanisms proposed to be common factors in Down syndrome (DS) and Alzheimer disease (AD) neuropathology, deficits in protein quality control have emerged as a unifying mechanism of neurodegeneration. Considering that disturbance of protein degradative systems are present in DS and that oxidized/misfolded proteins require...
Article
Protein phosphorylation of serine, threonine, and tyrosine residues is one of the most prevalent post-translational modifications fundamental in mediating diverse cellular functions in living cells. Aberrant protein phosphorylation is currently recognized as a critical step in the pathogenesis and progression of Alzheimer disease (AD). Changes in t...
Article
Objectives: oxidative stress is undoubtedly one of the main players in abdominal aortic aneurysm (AAA) pathophysiology. Recent studies in AAA patients reported an increase in the indices of oxidative damage at the tissue level and in biological fluids coupled with the loss of counter-regulatory mechanisms of protection from oxidative stress. We re...
Article
Down syndrome (DS) is the most common genetic cause of intellectual disability, resulting from trisomy of chromo