A5075326896- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Metabolism and Genetic Disorders
- Photosynthetic Processes and Mechanisms
- Retinal Development and Disorders
- Cancer, Hypoxia, and Metabolism
- Genetics and Neurodevelopmental Disorders
- Cell death mechanisms and regulation
- Genomics and Rare Diseases
- Autism Spectrum Disorder Research
- Genetic Neurodegenerative Diseases
- Genomic variations and chromosomal abnormalities
- Cerebrovascular and genetic disorders
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Connective tissue disorders research
- Drug-Induced Ocular Toxicity
- RNA regulation and disease
- GDF15 and Related Biomarkers
- Neurological diseases and metabolism
- Peroxisome Proliferator-Activated Receptors
- Endoplasmic Reticulum Stress and Disease
- Metabolomics and Mass Spectrometry Studies
- PI3K/AKT/mTOR signaling in cancer
- Caveolin-1 and cellular processes
Istituto delle Scienze Neurologiche di Bologna
2013-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2012-2020
Institute of Neurological Sciences
2012-2019
University of Bologna
2007-2015
Ospedale Bellaria
2015
Sapienza University of Rome
2012
Inserm
2012
Leber's hereditary optic neuropathy is a maternally inherited blinding disease caused as result of homoplasmic point mutations in complex I subunit genes mitochondrial DNA. It characterized by incomplete penetrance, only some mutation carriers become affected. Thus, the DNA necessary but not sufficient to cause neuropathy. Environmental triggers and genetic modifying factors have been considered explain its variable penetrance. We measured copy number mass indicators blood cells from...
OPA1 is a GTPase that controls mitochondrial fusion, cristae integrity, and mtDNA maintenance. In humans, eight isoforms are expressed as combinations of long short forms, but it unclear whether functions associated with specific and/or domains. To address this, we each the or different constructs isoform 1 in Opa1−/− MEFs. We observed any could restore structure, abundance, energetic efficiency independently network morphology. Long forms supported fusion; were better able to efficiency....
Dysfunctions in mitochondrial dynamics and metabolism are common pathological processes associated with Parkinson's disease (PD). It was recently shown that an inherited form of PD dementia is caused by mutations the OPA1 gene, which encodes for a key player fusion structure. iPSC-derived neural cells from these patients exhibited severe fragmentation, respiration impairment, ATP deficits, heightened oxidative stress. Reconstitution normal levels PD-derived normalized mitochondria morphology...
Leber's hereditary optic neuropathy (LHON) is the most frequent mitochondrial disease and was first to be genetically defined by a point mutation in DNA (mtDNA). A molecular diagnosis achieved up 95% of cases, vast majority which are accounted for 3 mutations within complex I subunit–encoding genes mtDNA (mtLHON). Here, we resolve enigma LHON absence pathogenic mutations. We describe biallelic nuclear encoded gene, DNAJC30, 33 unsolved patients from 29 families establish an autosomal...
Objective Mounting evidence links neurodegenerative disorders such as Parkinson disease and Alzheimer with mitochondrial dysfunction, recent emphasis has focused on dynamics quality control. Mitochondrial mtDNA maintenance is another link recently emerged, implicating mutations in the fusion genes OPA1 MFN2 pathogenesis of multisystem syndromes characterized by neurodegeneration accumulation multiple deletions postmitotic tissues. Here, we report 2 Italian families affected dominant chronic...
Abstract Leber’s hereditary optic neuropathy (LHON), the most frequent mitochondrial disease, is associated with DNA (mtDNA) point mutations affecting Complex I subunits, usually homoplasmic. This blinding disorder characterized by incomplete penetrance, possibly related to several genetic modifying factors. We recently reported that increased biogenesis in unaffected mutation carriers a compensatory mechanism, which reduces penetrance. Also, environmental factors such as cigarette smoking...
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a fatal, recessive disease caused by mutations in the gene encoding thymidine phosphorylase, leading to reduced enzymatic activity, toxic nucleoside accumulation, and secondary mitochondrial DNA damage. Thymidine phosphorylase replacement has been achieved allogeneic hematopoietic stem cell transplantation, procedure hampered high mortality. Based on expression liver, 25-year-old severely affected patient underwent liver...
Inherited optic neuropathies include complex phenotypes, mostly driven by mitochondrial dysfunction. We report an atrophy spectrum disorder, including retinal macular dystrophy and kidney insufficiency leading to transplantation, associated with DNA (mtDNA) depletion without accumulation of multiple deletions. By whole-exome sequencing, we identified mutations affecting the single-strand binding protein (SSBP1) in 4 families dominant 1 recessive inheritance. show that SSBP1 patient-derived...
Leber's hereditary optic neuropathy (LHON), a disease associated with mitochondrial DNA mutation, is characterized by blindness due to degeneration of retinal ganglion cells (RGCs) and their axons, which form the nerve.We show that sustained pathological autophagy compartment-specific mitophagy activity affects LHON patient-derived cybrids, as well induced pluripotent-stem-cell-derived neurons.This variably counterbalanced compensatory mitobiogenesis.The aberrant quality control disrupts...
Idebenone, the only approved treatment for Leber hereditary optic neuropathy (LHON), promotes recovery of visual function in up to 50% patients, but we can neither predict nor understand non-responders. Idebenone is reduced by cytosolic NAD(P)H oxidoreductase I (NQO1) and directly shuttles electrons respiratory complex III, bypassing affected LHON. We show here that two polymorphic variants drastically reduce NQO1 protein levels when homozygous or compound heterozygous. This hampers...
Abstract Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with strong genetic component in which rare variants contribute significantly to risk. We performed whole genome and/or exome sequencing (WGS and WES) SNP-array analysis identify both sequence copy number (SNVs CNVs) 435 individuals from 116 ASD families. identified 37 potentially damaging de novo SNVs (pdSNVs) the cases ( n = 144). Interestingly, two of them (one stop-gain one missense variant) occurred same...
Contribution to epileptic encephalopathy (EE) of mutations in CACNA2D2, encoding α2δ-2 subunit Voltage Dependent Calcium Channels, is unclear. To date only one CACNA2D2 mutation altering channel functionality has been identified a single family. In the same family, rare CELSR3 polymorphism also segregated with disease. Involvement EE therefore not confirmed, while that questionable. patient epilepsy, dyskinesia, cerebellar atrophy, psychomotor delay and dysmorphic features, offspring...
Autosomal dominant cerebellar ataxia-deafness and narcolepsy (ADCA-DN) Hereditary sensory neuropathy with dementia hearing loss (HSN1E) are two rare, overlapping neurodegenerative syndromes that have been recently linked to allelic pathogenic mutations in the DNMT1 gene, coding for DNA (cytosine-5)-methyltransferase 1 (DNMT1). is enzyme responsible maintaining nuclear genome methylation patterns during replication repair, thus regulating gene expression. The ADCA-DN HSN1E affect foci...
Leber's hereditary optic neuropathy (LHON) is a maternally inherited blinding disease characterized by degeneration of retinal ganglion cells (RGCs) and consequent nerve atrophy. Peculiar features LHON are incomplete penetrance gender bias, with marked male prevalence. Based on the different hormonal metabolism between genders, we proposed that estrogens play protective role in females showed these hormones ameliorate mitochondrial dysfunction through estrogen receptors (ERs). We also ERβ...
Mitochondrial diseases are highly heterogeneous metabolic disorders caused by genetic alterations in the mitochondrial DNA (mtDNA) or nuclear genome. In this study, we investigated a panel of blood biomarkers cohort 123 patients, with prominent neurological and muscular manifestations. These included creatine, fibroblast growth factor 21 (FGF21) growth/differentiation 15 (GDF-15), novel cell free circulating-mtDNA (ccf-mtDNA). All were significantly increased patient group. After...
We here report on the existence of Leber’s hereditary optic neuropathy (LHON) associated with peculiar combinations individually non-pathogenic missense mitochondrial DNA (mtDNA) variants, affecting MT-ND4, MT-ND4L and MT-ND6 subunit genes Complex I. The pathogenic potential these mtDNA haplotypes is supported by multiple evidences: first, LHON phenotype strictly inherited along maternal line in one very large family; second, variants are unique to two lineages that characterized recurrence...
Report13 April 2015Open Access Homozygous NOTCH3 null mutation and impaired signaling in recessive early-onset arteriopathy cavitating leukoencephalopathy Tommaso Pippucci U.O. Genetica Medica, Policlinico Sant'Orsola-Malpighi, Bologna, Italy Dipartimento di Scienze Mediche Chirurgiche (DIMEC), University of Search for more papers by this author Alessandra Maresca IRCCS Istituto delle Neurologiche Unita' Neurologia, Biomediche e Neuromotorie (DIBINEM), Pamela Magini Giovanna Cenacchi...