A5025900691- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Genetic Neurodegenerative Diseases
- Endoplasmic Reticulum Stress and Disease
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Muscle Physiology and Disorders
- Parkinson's Disease Mechanisms and Treatments
- Histone Deacetylase Inhibitors Research
- Alzheimer's disease research and treatments
- Genetics and Neurodevelopmental Disorders
- RNA regulation and disease
- Pharmacological Receptor Mechanisms and Effects
- Cellular transport and secretion
- Retinal Development and Disorders
- RNA modifications and cancer
- Inflammasome and immune disorders
- Cholinesterase and Neurodegenerative Diseases
- Curcumin's Biomedical Applications
- Autophagy in Disease and Therapy
- Intracerebral and Subarachnoid Hemorrhage Research
- Heat shock proteins research
- Cancer therapeutics and mechanisms
- Metabolism and Genetic Disorders
Columbia University
2023-2025
RWTH Aachen University
2014-2023
University of Modena and Reggio Emilia
2023
Universitätsklinikum Aachen
2015-2023
Weatherford College
2022
Leoni (Germany)
2022
Devi Ahilya Vishwavidyalaya
2020
Maastricht University
2018
Amsterdam University Medical Centers
2018
University of Amsterdam
2018
Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease. Cytoplasmic fused in sarcoma (FUS) aggregates are pathological hallmarks of FUS-ALS. Proper shuttling between nucleus and cytoplasm essential for physiological cell function. However, initial event pathophysiology FUS-ALS remains enigmatic. Using human induced pluripotent stem (hiPSCs)-derived neurons (MNs), we show that impairment poly(ADP-ribose) polymerase (PARP)-dependent DNA damage response (DDR) signaling...
Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of motoneurons in cerebral cortex, brainstem and spinal cord. Neuroinflammation plays an important role pathogenesis ALS involves activation microglia astrocytes. Intracellular inflammasome complexes are part innate immunity as they sense execute host inflammatory responses. The best component NLRP3 comprised NLR protein NLRP3, adaptor ASC pro-caspase 1. critical for caspase 1 processing release IL1β IL18. In this...
A major hallmark of the polyglutamine diseases is formation neuronal intranuclear inclusions disease proteins that are ubiquitinated and often associated with various chaperones proteasome components. But, how degraded by proteasomes not known. Here, we demonstrate CHIP (C terminus Hsp70-interacting protein) co-immunoprecipitates polyglutamine-expanded huntingtin or ataxin-3 associates their aggregates. Transient overexpression increases ubiquitination rate degradation ataxin-3. Finally,...
Intracellular accumulations of mutant, misfolded proteins are major pathological hallmarks amyotrophic lateral sclerosis (ALS) and related disorders. Recently, mutations in Sigma receptor 1 (SigR1) have been found to cause a form ALS frontotemporal lobar degeneration (FTLD). Our goal was pinpoint alterations modifications SigR1 determine how these changes contribute the pathogenesis ALS. In present study, we that levels protein were reduced lumbar patient spinal cord. abnormally accumulated...
Amyotrophic lateral sclerosis (ALS) is a lethal disease characterized by motor neuron degeneration and associated with aggregation of nuclear RNA-binding proteins (RBPs), including FUS. How FUS neurodegeneration are prevented in healthy neurons remain critically unanswered questions. Here, we use combination ALS patient autopsy tissue induced pluripotent stem cell-derived to study the effects mutations on RBP homeostasis. We show that FUS' tendency aggregate normally buffered interacting...
Article19 March 2021Open Access Source DataTransparent process Hsp90-mediated regulation of DYRK3 couples stress granule disassembly and growth via mTORC1 signaling Laura Mediani Department Biomedical, Metabolic Neural Sciences, Centre for Neuroscience Nanotechnology, University Modena Reggio Emilia, Modena, Italy Search more papers by this author Francesco Antoniani ItalyThese authors are contributed equally to work as second, third Veronica Galli Jonathan Vinet Genomic Post-Genomic Center,...
Aspirin and other nonsteroidal anti-inflammatory drugs inhibit cell proliferation induce apoptosis in various cancer lines, which is considered to be an important mechanism for their anti-tumor activity prevention of carcinogenesis. However, the molecular mechanisms through these compounds are not well understood. Here we have found that aspirin treatment mouse Neuro 2a cells impaired proteasome function caused severe mitochondrial abnormalities. Treatment with lead a dose- time-dependent...
Huntington's disease (HD) is a fatal neurodegenerative disorder. Despite tremendous effort to develop therapeutic tools in several HD models, there no effective cure at present. Acidosis has been observed previously cellular and vivo models as well the brains of patients. Here we challenged with amiloride (Ami) derivative benzamil (Ben), chemical agent used rescue acid-sensing ion channel (ASIC)-dependent acidotoxicity, examine whether chronic acidosis an important part pathomechanism these...
Huntington disease (HD) is a fatal hereditary neurodegenerative caused by an expansion of the polyglutamine (polyQ) stretch in huntingtin (htt). Whereas pathological significance expanded polyQ has been clearly established and tremendous effort to develop therapeutic tools for HD exerted, there yet no effective cure. many molecules able reduce accumulation aggregation have identified, including several Rho kinase (ROCK) inhibitors, it remains very important determine mechanism action...
Cells are equipped with an efficient quality control system to selectively eliminate abnormally folded and damaged proteins. Initially the cell tries refold unfolded proteins help of molecular chaperones, failure leads their degradation by ubiquitin proteasome system. But how this proteolytic machinery recognizes is poorly understood. Here, we report that E6-AP, a HECT domain family ligase implicated in Angelman syndrome, interacts substrate binding Hsp70/Hsc70 chaperones promotes chaperone...
Abstract Intracellular accumulations of altered, misfolded proteins in neuronal and other cells are pathological hallmarks shared by many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Mutations several genes give rise to familial forms ALS. Sigma receptor 1 have been found cause a juvenile form ALS frontotemporal lobar degeneration (FTLD). We recently described altered localization, abnormal modification loss function SigR1 sporadic In order further elucidate the...
Amyotrophic lateral sclerosis (ALS) is characterized by the selective degeneration of motor neurons (MNs) and their target muscles. Misfolded proteins which often form intracellular aggregates are a pathological hallmark ALS. Disruption functional interplay between protein degradation (ubiquitin proteasome system autophagy) RNA-binding homeostasis has recently been suggested as an integrated model that merges several ALS-associated into common pathophysiological pathway. The E102Q mutation...
Abstract Objective Mutations in Fused Sarcoma ( FUS or TLS ) are the fourth most prevalent Western European familial amyotrophic lateral sclerosis (ALS) populations and have been associated with causing both early very late disease onset. aggregation, DNA repair deficiency, genomic instability contributors to pathophysiology of FUS‐ALS, but their clinical significance per se influence on variability yet be sufficiently investigated. The aim this study was analyze genotype–phenotype...
Cytosolic aggregation of the RNA binding protein TDP-43 (transactive response DNA-binding 43) is a hallmark amyotrophic lateral sclerosis and frontotemporal dementia. Here, we report that during oxidative stress, becomes SUMO2/3-ylated by SUMO E3 ligase PIAS4 (protein inhibitor activated STAT 4) enriches in cytoplasmic stress granules (SGs). Upon pharmacological inhibition SUMO2/3-ylation or depletion, enrichment SGs accompanied irreversible aggregation. In cells are unable to assemble SGs,...
Abstract Oligodendrocytes are integral to efficient neuronal signaling. Loss of myelinating oligodendrocytes is a central feature many neurological diseases, including multiple sclerosis (MS). The results neuropathological studies suggest that react with differing sensitivity toxic insults, some cells dying early during lesion development and being resistant for weeks. This proposed graded vulnerability has never been demonstrated but provides an attractive window therapeutic interventions....
Abstract ER stress signaling is linked to the pathophysiological and clinical disease manifestations in amyotrophic lateral sclerosis (ALS). Here, we have investigated stress-induced adaptive mechanisms C9ORF72 -ALS/FTD, focusing on uncovering early endogenous neuroprotective crosstalk between pathological responses onset progression. We provide evidence for of stress-mediated response patient-derived motoneurons (MNs), reflected by elevated increase GRP75 expression. These transiently...
Dysregulation of growth factor receptors such as the epidermal receptor (EGFR) and its truncated form EGFRvIII is frequently found in human tumors. a promising target for selective molecular tumor therapy because it exclusively expressed by cells. Cetuximab/Erbitux monoclonal antibody which targets EGFR EGFRvIII. The effects cetuximab on but still exact function mechanism relation to are incompletely understood. Therefore, we investigated influence signaling cellular survival. We that leads...
Abstract Background Huntington's Disease (HD) is a fatal hereditary neurodegenerative disease caused by the accumulation of mutant huntingtin protein (Htt) containing an expanded polyglutamine (polyQ) tract. Activation channel responsible for inositol-induced Ca 2+ release from ensoplasmic reticulum (ER), was found to contribute substantially neurodegeneration in HD. Importantly, chemical and genetic inhibition inositol 1,4,5-trisphosphate (IP3) receptor type 1 (IP3R1) has been shown reduce...