Andrea Stoccoro

• PhD
• PostDoc Position at University of Pisa

Neurodegenerative diseases are characterized by profound differences between females and males in terms of incidence, clinical presentation, and disease progression. Furthermore, there is evidence suggesting that differences in sensitivity to medical treatments may exist between the two sexes. Although the role of sex hormones and sex chromosomes i...

Individuals affected by neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), are dramatically increasing worldwide. Thus, several efforts are being made to develop strategies for stopping or slowing the spread of these illnesses. Although causative genetic variants linked...

Background/Objectives: One-carbon metabolism is a critical pathway for epigenetic mechanisms. Circulating biomarkers of one-carbon metabolism have been associated with changes in nuclear DNA methylation levels in individuals affected by age-related diseases. More and more studies are showing that even mitochondrial DNA (mtDNA) could be methylated....

Aim: To correlate mitochondrial D-loop region methylation levels and mtDNA copy number with disease duration in familial amyotrophic lateral sclerosis (ALS) patients. Patients & methods: The study population included 12 ALS patients with a mutation in SOD1 and 13 ALS patients with the C9orf72 hexanucleotide repeat expansion. Methylation levels of t...

The central objective of the metamorphosis of discovery science into biomedical applications is to serve the purpose of patients and curtail the global disease burden. The journey from the discovery of DNA methylation (DNAm) as a biological process to its emergence as a diagnostic tool is one of the finest examples of such metamorphosis and has tak...

Autism spectrum disorder (ASD) refers to a neurodevelopmental condition whose detection still remains challenging in young females due to the heterogeneity of the behavioral phenotype and the capacity of camouflage. The availability of quantitative biomarkers to assess brain function may support in the assessment of ASD. Functional Near-infrared Sp...

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition, the underlying pathological mechanisms of which are not yet completely understood. Although several genetic and genomic alterations have been linked to ASD, for the majority of ASD patients, the cause remains unknown, and the condition likely arises due to complex interaction...

Autism spectrum disorder ( is a genetically heterogeneous disorder and may be caused by both inherited and de novo gene variants Increasing evidence points to a contribution of environmental and epigenetic factors in ASD, but their connections are still largely unexplored Aim of the present pilot study was to apply the Auto Contractive Map algorith...

Exposure to environmental stressors during pregnancy plays an important role in influencing subsequent susceptibility to certain chronic diseases through the modulation of epigenetic mechanisms, including DNA methylation. Our aim was to explore the connections between environmental exposures during gestation with DNA methylation of placental cells,...

Neurodevelopmental Disorders (NDs) are a heterogeneous group of disorders and are considered multifactorial diseases with both genetic and environmental components. Epigenetic dysregulation driven by adverse environmental factors has recently been documented in neurodevelopmental disorders as the possible etiological agent for their onset. However,...

Background: Adolescent idiopathic scoliosis (AIS), affecting 2–4% of adolescents, is a multifactorial spinal disease. Interactions between genetic and environmental factors can influence disease onset through epigenetic mechanisms, including DNA methylation, histone modifications and miRNA expression. Recent evidence reported that, among all clinic...

Dietary factors can regulate epigenetic processes during life, modulating the intracellular pools of metabolites necessary for epigenetic reactions and regulating the activity of epigenetic enzymes. Their effects are strong during the prenatal life, when epigenetic patterns are written, allowing organogenesis. However, interactions between diet and...

Aim and methods: Artificial neural networks were used to unravel connections among blood gene methylation levels, sex, maternal risk factors and symptom severity evaluated using the Autism Diagnostic Observation Schedule 2 (ADOS-2) score in 58 children with autism spectrum disorder (ASD). Results: Methylation levels of MECP2, HTR1A and OXTR genes w...

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and represents the leading cause of cognitive impairment and dementia in older individuals throughout the world. The main hallmarks of AD include brain atrophy, extracellular deposition of insoluble amyloid-β (Aβ) plaques, and the intracellular aggregation of protein tau in neurof...

Methylation levels of the mitochondrial displacement loop (D-loop) region have been reported to be altered in the brain and blood of Alzheimer’s disease (AD) patients. Moreover, a dynamic D-loop methylation pattern was observed in the brain of transgenic AD mice along with disease progression. However, investigations on the blood cells of AD patien...

Myasthenia gravis (MG) is a neuromuscular autoimmune disease characterized by prevalence in young women (3:1). Several mechanisms proposed as explanations for gender bias, including skewed X chromosome inactivation (XCI) and dosage or sex hormones, are often involved in the development of autoimmunity. The skewed XCI pattern can lead to an unbalanc...

The aim of the project is to investigate the connections among in utero exposure to various environmental stressors and gene-specific and global methylation levels, in DNA from placenta tissue and mother and infant buccal swab cells, by applying fourth generations Artificial Neural Networks (ANNs) able to create semantic connectivity maps.

Aim: To detect early-life environmental factors leading to DNA methylation changes of autism spectrum disorder (ASD)-related genes in young ASD females and reveal epigenetic biomarkers of disease severity. Materials & methods: We investigated blood methylation levels of MECP2, OXTR, BDNF, RELN, BCL2, EN2 and HTR1A genes in 42 ASD females. Results:...

Many complex traits or diseases, such as infectious and autoimmune diseases, cancer, xenobiotics exposure, neurodevelopmental and neurodegenerative diseases, as well as the outcome of vaccination, show a differential susceptibility between males and females. In general, the female immune system responds more efficiently to pathogens. However, this...

Altered mitochondrial DNA (mtDNA) methylation has been detected in several human pathologies, although little attention has been given to neurodegenerative diseases. Recently, altered methylation levels of the mitochondrial displacement loop (D-loop) region, which regulates mtDNA replication, were observed in peripheral blood cells of Alzheimer’s d...

Epigenetic modifications of the nuclear genome, including DNA methylation, histone modifications and non-coding RNA post-transcriptional regulation, are increasingly being involved in the pathogenesis of several human diseases. Recent evidence suggests that also epigenetic modifications of the mitochondrial genome could contribute to the etiology o...

The wide spectrum of unique needs and strengths of Autism Spectrum Disorders (ASD) is a challenge for the worldwide healthcare system. With the plethora of information from research, a common thread is required to conceptualize an exhaustive pathogenetic paradigm. The epidemiological and clinical findings in ASD cannot be explained by the tradition...

The wide spectrum of unique needs and strengths of Autism Spectrum Disorders (ASD) is a challenge for the worldwide healthcare system. With the plethora of information from research, a common thread is required to conceptualize an exhaustive pathogenetic paradigm. The epidemiological and clinical findings in ASD cannot be explained by the tradition...

Epigenetic marks, such as DNA methylation and histone modifications, play a fundamental role in the neuronal plasticity required for learning and memory. As a consequence, changes of the epigenetic landscape can contribute to the age-related cognitive decline as well as to cognitive impairment and neurodegeneration. This chapter describes the avail...

A feature of thymomas is their frequent association with myasthenia gravis (MG), an autoimmune disease characterized by the production of autoantibodies directed to different targets at the neuromuscular junction. Indeed, almost 30-40% of thymomas are found in patients with a type of MG termed thymoma-associated MG (TAMG). Recent studies suggest th...

Background: Mitochondrial dysregulation and aberrant epigenetic mechanisms have been frequently reported in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), and several researchers suggested that epigenetic dysregulation in mitochondrial DNA (mtDNA) could contribute to the neurodegenerative process. We recently screened f...

Aim: To assess promoter methylation levels, gene expression levels and 677C>T/1298A>C genotype and allele frequencies of the MTHFR gene in 45 mothers of attention-deficit/hyperactivity disorder affected child/children (ADHDM) and compare it with age matched healthy control mothers (HCM). Materials & methods: High resolution melting analysis, quanti...

Aim: Impaired methylation of the mitochondrial DNA and particularly in the regulatory displacement loop (D-loop) region, is increasingly observed in patients with neurodegenerative disorders. The present study aims to investigate if common polymorphisms of genes required for one-carbon metabolism ( MTHFR, MTRR, MTR and RFC-1) and DNA methylation re...

Background Hypermethylation of the growth hormone secretagogue receptor gene (GHSR) is increasingly observed in human cancers, suggesting that it could represent a pan-cancer biomarker of clinical interest. However, little is still known concerning GHSR methylation levels in thymic epithelial tumors, and particularly in thymomas from patients with...

The Presenilin1 (PSEN1) gene encodes the catalytic peptide of the γ-secretase complex, a key enzyme that cleaves the amyloid-β protein precursor (AβPP), to generate the amyloid-β (Aβ) peptides, involved in Alzheimer’s Disease (AD). Other substrates of the γ-secretase, such as E-cadherin and Notch1, are involved in neurodevelopment and haematopoiesi...

DNA methyltransferase 1 (DNMT1) is responsible for the maintenance of DNA methylation patterns during cell division. Several human diseases are characterized by impaired DNMT1 gene methylation, but less is known about the factors that regulate DNMT1 promoter methylation levels. Dietary folates and related B-vitamins are essential micronutrients for...

Methylenetetrahydrofolate reductase (MTHFR) is a pivotal enzyme in the one-carbon metabolism, a metabolic pathway required for DNA synthesis and methylation reactions. MTHFR hypermethylation, resulting in reduced gene expression, can contribute to several human disorders, but little is still known about the factors that regulate MTHFR methylation l...

Mitochondrial impairment and increased oxidative stress are common features in neurodegenerative disorders, leading researchers to speculate that epigenetic changes in the mitochondrial DNA (mitoepigenetics) could contribute to neurodegeneration. The few studies performed so far to address this issue revealed impaired methylation levels of the mito...

Congenital myotonic dystrophy type 1 (CDM1) is characterized by severe symptoms that affect patients from birth, with 40% mortality in the neonatal period and impaired skeletal muscle development. In this paper, we examined the relationship between autophagy and abnormal myogenic differentiation of CDM1 myoblasts. We investigated these pathological...

Aim: To investigate mitochondrial DNA (mtDNA) copy number and D-loop region methylation in carriers of SOD1, TARDBP, FUS and C9orf72 mutations. Methods: Investigations were performed in blood DNA from 114 individuals, including amyotrophic lateral sclerosis (ALS) patients, presymptomatic carriers and noncarrier family members. Results: Increas...

Aim: To investigate GHSR and GHRL methylation in 73 pairs of colorectal cancer (CRC) tissues and healthy adjacent mucosa. Methods: Methylation was assessed with methylation-sensitive high-resolution melting. Results: GHSR was significantly hypermethylated in CRC tissues than in healthy mucosa (p < 1 × 10-5), but no significant changes of GHRL...

Advances in molecular biology technologies have allowed uncovering the role of epigenetic regulation in several complex diseases, such as cancer and neurodegenerative disorders. Although the role of epigenetic mechanisms in Alzheimer's disease is still little understood, recent findings clearly show that such mechanisms are dysregulated during dise...

Purpose: Epigenetic traits are influenced by clinical variables; interaction between DNA methylation (DNAmeth) and bariatric surgery-induced weight loss has been scarcely explored. We investigated whether DNAmeth of genes encoding for molecules/hormones regulating appetite, food intake or obesity could predict successful weight outcome following R...

Objective: More than 180 different superoxide dismutase 1 (SOD1) mutations have been described to date in amyotrophic lateral sclerosis (ALS) patients, including not completely penetrant ones leading to phenotypic heterogeneity among carriers. We collected DNA samples from five ALS families with not fully penetrant SOD1 mutations (p.Asn65Ser, p.Gly...

Mitochondrial impairment is a feature of neurodegeneration and many investigators have suggested that epigenetic modifications of the mitochondrial DNA (mtDNA) might be involved in late-onset Alzheimer’s disease (LOAD), but evidence in humans is limited. We assessed the methylation levels of the mtDNA D-loop region in blood DNA from 133 LOAD patien...

Titanium dioxide nanoparticles (TiO2 NP) are broadly used in a wide range of applications. Several studies have reported that TiO2 NP possess cytotoxic and genotoxic properties that could induce adverse health effects in humans. The FP7 Sanowork project was aimed to minimize occupational hazard and exposure to engineered nanomaterials (ENM), includ...

Background: A functional polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, namely C677T (rs1801133), results in increased Hcy levels and has been associated with risk of late-onset Alzheimer’s disease (LOAD). Many investigators reported association between rs1801133 and LOAD risk in Asian populations and in carriers of the apoli...

Background: There is increasing interest in DNA methylation studies in Alzheimer’s disease (AD), but little is still known concerning the relationship between gene-promoter methylation and circulating biomarkers of one-carbon metabolism in patients. Objective: To detect the connections among circulating folate, homocysteine (hcy) and vitamin B12 le...

The FP7 Sanowork project was aimed to minimise occupational hazard and exposure to engineered nanomaterials (ENM) through the surface modification in order to prevent possible health effects. In this frame, a number of nanoparticles (NP) have been selected, among which zirconium (ZrO2) and titanium (TiO2) dioxide. In this study, we tested ZrO2NP an...

There is substantial evidence of impaired DNA repair activities in Alzheimer's disease (AD) neurons and peripheral tissues, inducing some investigators to speculate that this could partially result from promoter hypermethylation of DNA repair genes, resulting in gene silencing in those tissues. In the present study a screening cohort composed by la...

Increasing evidence points to an epigenetic contribution in Alzheimer's disease (AD) pathogenesis. In this regard, variants and polymorphisms of DNA methyltransferase genes (DNMTs) are being investigated for their contribution to cognitive decline and dementia, but results are still scarce or controversial. In the present study we genotyped 710 Cau...

Arsenic is a human carcinogen with weak mutagenic properties that induces tumors through mechanisms not yet completely understood. People worldwide are exposed to arsenic-contaminated drinking water, and epidemiological studies showed a high percentage of lung, bladder, liver, and kidney cancer in these populations. Several mechanisms by which arse...

There is increasing interest in the development of cost-effective techniques for the quantification of DNA methylation biomarkers. We analyzed 90 samples of surgically resected colorectal cancer tissues for APC and CDKN2A promoter methylation using methylation sensitive-high resolution melting (MS-HRM) and pyrosequencing. MS-HRM is a less expensive...

The term epigenetics includes several phenomena such as DNA methylation, histone tail modifications, and microRNA mediated mechanisms, which are able to mold the chromatin structure and/or gene expression levels, without altering the primary DNA sequence. Environmental agents can exert epigenetic properties and there is increasing evidence of epige...