A5070339372- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- Genetics and Neurodevelopmental Disorders
- Glioma Diagnosis and Treatment
- interferon and immune responses
- Connective tissue disorders research
- Congenital heart defects research
- Machine Learning in Bioinformatics
- Drug Transport and Resistance Mechanisms
- Moyamoya disease diagnosis and treatment
- Diet and metabolism studies
- Genomic variations and chromosomal abnormalities
- Extracellular vesicles in disease
- Pharmacological Effects and Toxicity Studies
- Amyotrophic Lateral Sclerosis Research
- Cell death mechanisms and regulation
- Drug-Induced Ocular Toxicity
- Microtubule and mitosis dynamics
- Prion Diseases and Protein Misfolding
- Genomics and Rare Diseases
- Chemokine receptors and signaling
- Congenital Ear and Nasal Anomalies
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer, Hypoxia, and Metabolism
- Advanced MRI Techniques and Applications
Fondazione IRCCS Istituto Neurologico Carlo Besta
2015-2025
Italian institute for Genomic Medicine
2018
Epilepsy is a frequent symptom in patients with glioma. Although treatment antiepileptic drugs generally effective controlling seizures, drug-resistant are not uncommon. Multidrug resistance proteins (MRPs) and P-gp over-represented brain tissue of epilepsy, suggesting their involvement the clearance medications. In addition to anticonvulsant action, some have been documented for cytotoxic effects. Aim this study was evaluate possible vitro effects two new-generation on human glioma cell...
Abstract Background In recent years, the seed amplification assay (SAA) has enabled identification of pathological TDP-43 in cerebrospinal fluid (CSF) and olfactory mucosa (OM) patients with genetic forms frontotemporal dementia (FTD) amyotrophic lateral sclerosis (ALS). Here, we investigated seeding activity OM samples collected from sporadic ALS. Methods were (a) motor neuron diseases (MND), including spinal ALS ( n = 35), bulbar 18), primary 10), facial onset sensory neuronopathy 2); (b)...
ZC4H2 is involved in human brain development, and, if mutated, can be responsible for a rare X-linked disorder, originally presented literature as Wieacker-Wolff syndrome and Miles-Carpenter syndrome. In males, severe intellectual disability associated with variable symptoms of central peripheral nervous system involvement, such spasticity, hyperreflexia, muscle weakness, arthrogryposis. Female carriers are usually described asymptomatic or only mildly affected. Here, we report on girl...
Metastatic brain disease (MBD) has seen major advances in clinical management, focal radiation therapy approaches and knowledge of biological factors leading to improved prognosis. Extracellular vesicles (EVs) have been found play a role tumor cross-talk with the target organ, contributing formation premetastatic niche. Human lung breast cancer cell lines were characterized for adhesion molecule expression used evaluate their migration ability an vitro model. Conditioned culture media...
We developed an in vitro contact through-feet blood brain barrier (BBB) model built using type IV collagen, rat astrocytes, and human umbilical vein endothelial cells (HUVECs) cocultured through Transwell porous polycarbonate membrane. The between astrocytes HUVECs was demonstrated by electron microscopy: endfeet pass the 8.0 μ m pores inducing to assume a cerebral phenotype. Using this we evaluated transmigration of melanoma from two different patients (M1 M2) selected among seven primary...
Leber's Hereditary Optic Neuropathy (LHON) is a maternally inherited disorder caused by homoplasmic mutations of mitochondrial DNA (mtDNA). LHON characterized the selective degeneration retinal ganglion cells (RGC). Almost all maternal lineages are mutant (100% mtDNA copies mutant) for one three frequent now found in over 90% patients worldwide (m.11778G > A/MT-ND4, m.3460G A/MT-ND1, m.14484 T C/MT-ND6). Human induced pluripotent stem (hiPSCs) were generated from patient carrying A/MT-ND1...
Glioblastoma multiforme (GBM) is considered the most malignant form of primary brain tumor. Despite multimodal treatment, prognosis remains poor. Ketogenic diet (KD) has been suggested for treatment GBM. In this study, syngenic, orthotopic GL261 mouse glioma model was used to evaluate effects KD on metabolic responses tumor using 7T magnetic resonance imaging/spectroscopy. cells were injected into caudate nucleus mice. Following implantation, animals fed with standard chow or underwent a KD....
Abstract The NF-kB family of transcription factors is up-regulated in inflammation and different cancers. Recent data described heterozygous deletions the Inhibitor alpha gene ( NFKBIA ) about 20% glioblastomas (GBM): were mutually exclusive with epidermal growth factor receptor EGFR amplification, a frequent event GBM. We assessed status 69 primary GBMs corresponding neurospheres (NS). deletion was investigated by copy number variation assay (CNV); amplification CNV ratio HGF ; expression...
Autoinflammatory diseases are rare illnesses characterized by apparently unprovoked inflammation without high-titer auto-antibodies or antigen-specific T cells. They may cause neurological manifestations, such as meningitis and hearing loss, but they also non-neurological manifestations. In this work we studied a 30-year-old man who had chronic disease meningitis, progressive persistently raised inflammatory markers diffuse leukoencephalopathy on brain MRI. He suffered from recurrent...
The generation of inducible pluripotent stem cells (iPSCs) is a revolutionary technique allowing production patient-specific cell lines used for disease modeling, drug screening, and therapy. Integrity nuclear DNA (nDNA) mandatory to allow iPSCs utilization, while quality control mitochondrial (mtDNA) rarely included in the validation process. In this study, we performed mtDNA deep sequencing during transition from parental fibroblasts reprogrammed iPSC differentiated neuronal precursor...
Leber hereditary optic neuropathy (LHON) is one of the most common mitochondrial illness, causing retinal ganglion cell degeneration and central vision loss. It stems from point mutations in DNA (mtDNA), with key being m.3460G > A, m.11778G m.14484 T C. Fibroblasts identical twins, sharing C m.10680G A variants each 70 % heteroplasmy, were used to generate iPSC lines. Remarkably, twin, a LHON patient, displayed symptoms, while other, carrier, remained asymptomatic. These iPSCs offer valuable...
The presence of redundant copy number variants (CNVs) in groups patients with neurological diseases suggests that these could have pathogenic effect. We collected array comparative genomic hybridization (CGH) data about 2,500 affected by neurocognitive disorders and we observed CNVs 2p16.3 locus were as frequent those 15q11.2, being both the most unbalances our cohort patients. Focusing to region, involving NRXN1 coding region been already associated neuropsychiatric disorders, although...
Moyamoya angiopathy (MA) is a cerebrovascular disease determining progressive stenosis of the terminal part internal carotid arteries (ICAs) and their proximal branches compensatory development abnormal "moyamoya" vessels. MA occurs as an isolated cerebral (so-called moyamoya disease) or in association with various conditions (moyamoya syndromes) including several heritable such Down syndrome, neurofibromatosis type 1 other genomic defects. Although mechanism that links to these genetic...
Pearson marrow pancreas syndrome (PMPS) is a sporadic mitochondrial disease, resulting from the clonal expansion of mutated DNA (mtDNA) molecule bearing macro-deletion, and therefore missing essential genetic information. PMPS characterized by presence deleted (Δ) mtDNA that co-exist with variable amount wild-type mtDNA, condition termed heteroplasmy. All tissues affected individual, including haemopoietic system post-mitotic, highly specialized (brain, skeletal muscle, heart) contain...
RATIONAL AND AIMS: Epilepsy is a frequent side effect in patients with glioma. Although treatment antiepileptic drugs generally effective controlling seizures, drug-resistant patient are not uncommon. Multidrug resistance proteins (MRPs) and P-gp over-represented brain tissue of epilepsy affected suggesting their involvement the clearance medications. In addition to action anticonvulsant has been documented for some possible cytotoxic effect. METHODS: The vitro effects two new generation...
Abstract BACKGROUND Meningioma is the most common primary tumor of CNS, usually a benign (grade I) successfully treated by surgical resection, while in 25–30% cases more aggressive neoplasm with high recurrence rate and poor prognosis II-III). In last years some studies tried to investigate genomic profile meningioma find additional prognostic factors potential therapeutic targets. Aim our study was use array-CGH (aCGH) possible indicators risk meningiomas. MATERIAL AND METHODS We...
Abstract Glioblastoma multiforme is the most malignant subtype of brain tumor. Despite multimodal treatment (surgical resection and chemo/radiotherapy) prognosis remains unsatisfactory. Based on Warburg hypothesis, ketogenic diet (KD) has been suggested in GBM. The syngenic, orthotopic GL261 mouse glioma model was used to evaluate effects KD 7T magnetic resonance imaging/spectroscopy metabolic response tumor diet. Mice were injected with 10^5 cells into caudate nucleus. Following...