A5027952986- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Sphingolipid Metabolism and Signaling
- Endoplasmic Reticulum Stress and Disease
- Neuroinflammation and Neurodegeneration Mechanisms
- Vestibular and auditory disorders
- Atherosclerosis and Cardiovascular Diseases
- Microtubule and mitosis dynamics
- Glycosylation and Glycoproteins Research
- Cellular transport and secretion
- Parkinson's Disease Mechanisms and Treatments
- Lipid metabolism and disorders
- Tryptophan and brain disorders
- Botulinum Toxin and Related Neurological Disorders
- Genetics and Neurodevelopmental Disorders
- Neurological diseases and metabolism
- Lysosomal Storage Disorders Research
- Hearing, Cochlea, Tinnitus, Genetics
- CRISPR and Genetic Engineering
- Neurological disorders and treatments
- Genetics, Aging, and Longevity in Model Organisms
- Chromatin Remodeling and Cancer
- Genomic variations and chromosomal abnormalities
- Lipid metabolism and biosynthesis
- Cancer, Hypoxia, and Metabolism
Istituto Neurologico Mediterraneo
2016-2024
Ospedale Versilia
2017-2024
Azienda Usl Toscana Centro
2022
Institute of Genetics and Biophysics
2016
Abstract Blood-brain barrier (BBB) breakdown, due to the concomitant disruption of tight junctions (TJs), normally required for maintenance BBB function, and altered transport molecules between blood brain vice-versa, has been suggested significantly contribute development progression different disorders including Huntington’s disease (HD). Although detrimental consequence breakdown may have in clinical settings, timing its alteration remains elusive many neurodegenerative diseases. In this...
Objective. We investigated the reliability and accuracy of a bedside diagnostic algorithm for patients presenting with vertigo/unsteadiness to emergency department. Methods. enrolled consecutive adult at tertiary hospital. STANDING, acronym four-step we have previously described, based on nystagmus observation well known manoeuvres, includes 1) discrimination between SponTAneous positional nystagmus, 2) evaluation Nystagmus Direction, 3) head Impulse test 4) equilibrium (staNdinG)....
Huntington's disease is characterized by a complex and heterogeneous pathogenic profile. Studies have shown that disturbance in lipid homeostasis may represent critical determinant the progression of several neurodegenerative disorders. The recognition perturbed metabolism only recently becoming evident HD. In order to provide more insight into nature such perturbation effect its modulation HD pathology, we investigated Sphingosine-1-phosphate (S1P), one most important bioactive lipids, both...
Alterations of lipid metabolism have been frequently associated with Huntington's disease (HD) over the past years. HD is most common neurodegenerative disorder, a complex pathogenic profile, typically characterized by progressive striatal and cortical degeneration motor, cognitive behavioral disturbances. Previous findings from our group support idea that disturbed sphingolipid could represent an additional hallmark disease. Although such defect represents biological denominator among...
Parkinson's disease (PD) represents the most common neurodegenerative movement disorder. We recently identified 16 novel genes associated with PD. In this study, we focused attention on and rare variants in lysosomal K+ channel TMEM175. The study includes a detailed clinical genetic analysis of 400 cases 300 controls. Molecular studies were performed patient-derived fibroblasts. functional properties mutant channels assessed by patch-clamp technique co-immunoprecipitation. have found that...
Huntington's disease (HD) is the most common neurodegenerative disorder for which no effective cure yet available.Although several agents have been identified to provide benefits so far, number of therapeutic options remains limited with only symptomatic treatment available.Over past few years, we demonstrated that sphingolipid-based approaches may open door new and more targeted treatments disease.In this study, investigated potential stimulating sphingosine-1-phosphate (S1P) receptor 5 by...
Huntington's disease (HD) has traditionally been described as a disorder purely of the brain; however, evidence indicates that peripheral abnormalities are also commonly seen. Among others, severe unintended body weight loss represents prevalent and often debilitating feature HD pathology, with no therapies available. It correlates progression significantly affects quality life patients. Curcumin, naturally occurring polyphenol multiple therapeutic properties, validated to exert important...
Although several agents have been identified to provide therapeutic benefits in Huntington Disease (HD), the number of conventionally used treatments remains limited and only symptomatic. Thus, it is plausible that need identify new targets for development alternative more effective becoming increasingly urgent. Recently, sphingosine-1-phosphate axis has reported be a valid potential novel molecular target therapy HD. Modulation aberrant metabolism S1P HD proved exert neuroprotective action...
Rett syndrome (RTT, online MIM 312750) is a devastating neurodevelopmental disorder characterized by motor and cognitive disabilities. It mainly caused pathogenetic variants in the X-linked MECP2 gene, encoding an epigenetic factor crucial for brain functioning. Despite intensive studies, RTT mechanism remains to be fully elucidated. Impaired vascular function has been previously reported mouse models; however, whether altered homeostasis subsequent blood–brain barrier (BBB) breakdown occur...
Identification of molecules able to promote neuroprotective mechanisms can represent a promising therapeutic approach neurodegenerative disorders including Huntington’s disease. Curcumin is an antioxidant and agent, even though its efficacy limited by poor absorption, rapid metabolism, systemic elimination, blood–brain barrier (BBB) permeability. Herein, we report on novel biodegradable curcumin-containing nanoparticles favor the compound delivery potentially enhance brain bioavailability....
The longevity-associated variant (LAV) of the bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) has been found significantly enriched in long-living individuals. Neuroinflammation is a key player Huntington's disease (HD), neurodegenerative disorder caused by neural death due to expanded CAG repeats encoding long polyglutamine tract huntingtin protein (Htt). Herein, we showed that striatal-derived cell lines with Htt (STHdh Q111/111) expressed and secreted lower...
Gliomas are the most common primary malignant brain tumors. Glioblastoma, IDH-wildtype (GBM, CNS WHO grade 4) is aggressive form of glioma and characterized by extensive hypoxic areas that strongly correlate with tumor malignancy. Hypoxia promotes several processes, including stemness, migration, invasion, angiogenesis, radio- chemoresistance, have direct impacts on treatment failure. Thus, there still an increasing need to identify novel targets limit GBM relapse. Polysialic acid (PSA) a...
Prominent pathological features of Huntington’s disease (HD) are aggregations mutated Huntingtin protein (mHtt) in the brain and neurodegeneration, which causes characteristic motor (such as chorea dystonia) non-motor symptoms. However, numerous systemic peripheral deficits HD have gained increasing attention recently, since those factors likely modulate progression, including pathology. While whole-body metabolic abnormalities organ-specific pathologies been relatively well described,...
Abstract Huntington’s disease (HD) is a neurodegenerative disorder caused by CAG-repeat expansions in the huntingtin ( HTT ) gene. The resulting mutant (mHTT) protein induces toxicity and cell death via multiple mechanisms no effective therapy available. Here, we employ genome-wide screening pluripotent mouse embryonic stem cells (ESCs) to identify suppressors of mHTT toxicity. Among identified suppressors, linked HD-associated processes, focus on Metal response element binding transcription...
Acute vertigo is defined as the perception of movement oneself or surroundings in absence actual motion and it a frequent cause for emergency department admissions. The utilization medical resources duration hospital stay this kind symptom high. Furthermore, efficiency brain imaging acute phase low, considering limited sensitivity both CT MRI diagnosing diseases that are causes central type vertigo. Relying on tests can provide false reassurance event negative results prolong in-hospital...
Emerging evidence indicates that Huntington's disease (HD) may be described as multi-organ pathology. In this context, we and others have contributed to demonstrate the is characterized by an impairment of homeostasis gastro-intestinal (GI) tract. Sphingolipids represent a class molecules involved in regulation maintenance different tissues organs including GI system. study, investigated whether alteration Sphingosine-1-phosphate (S1P) metabolism, previously human HD brains animal models,...
Alterations in the metabolism of sphingolipids, a class biologically active molecules cell membranes with direct effect on vascular homeostasis, are increasingly recognized as important determinant different disorders. However, it is not clear whether sphingolipids implicated pathogenesis hypertension-related cerebrovascular and renal damage. In this study, we evaluated existence possible abnormalities related to sphingolipid brain kidneys two well validated spontaneously hypertensive rat...
<h3>Background</h3> In the last decade, perturbed metabolism of some sialylated molecules has been described to play an essential role in pathogenesis Huntington's disease (HD). this context, we have contributed demonstrate that sialic-acid containing glycosphingolipids – gangliosides is impaired HD and its modulation results therapeutically effective pre-clinical models. Interestingly, evidence altered levels both sialo-glycoproteins suggests overall sialo-conjugates HD. <h3>Aims</h3> The...
Abstract Synaptic dysfunction is an early pathogenic event leading to cognitive decline in Huntington’s disease (HD). We previously reported that the active ADAM10 level increased HD cortex and striatum, causing excessive proteolysis of synaptic cell adhesion protein N-Cadherin. Conversely, inhibition neuroprotective prevents mice. Although breakdown cortico-striatal connection has been historically linked deterioration HD, dendritic spine loss long-term potentiation (LTP) defects identified...