A5050031542- Mitochondrial Function and Pathology
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Metabolism and Genetic Disorders
- Autophagy in Disease and Therapy
- Parkinson's Disease Mechanisms and Treatments
- Genetic Neurodegenerative Diseases
- Biochemical Acid Research Studies
- Pluripotent Stem Cells Research
- ATP Synthase and ATPases Research
- Diet and metabolism studies
- 3D Printing in Biomedical Research
- Nerve injury and regeneration
- Endoplasmic Reticulum Stress and Disease
- Neurological diseases and metabolism
- Epigenetics and DNA Methylation
- Redox biology and oxidative stress
- RNA regulation and disease
- interferon and immune responses
- Neurological disorders and treatments
- Amino Acid Enzymes and Metabolism
- Neuroscience and Neural Engineering
- Genetics and Neurodevelopmental Disorders
University of Milan
2024
Istituto Nazionale Genetica Molecolare
2024
Karolinska Institutet
2015-2021
Vita-Salute San Raffaele University
2021
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2021
Istituti di Ricovero e Cura a Carattere Scientifico
2021
Abstract Recent findings in human samples and animal models support the involvement of inflammation development Parkinson’s disease. Nevertheless, it is currently unknown whether microglial activation constitutes a primary event neurodegeneration. We generated new mouse model by lentiviral-mediated selective α-synuclein (αSYN) accumulation cells. Surprisingly, these mice developed progressive degeneration dopaminergic (DA) neurons without endogenous αSYN aggregation. Transcriptomics...
<h3>Background</h3> Coenzyme Q is an essential mitochondrial electron carrier, redox cofactor and a potent antioxidant in the majority of cellular membranes. deficiency has been associated with range metabolic diseases, as well some drug treatments ageing. <h3>Methods</h3> We used whole exome sequencing (WES) to investigate patients inherited diseases applied novel ultra-pressure liquid chromatography—mass spectrometry approach measure coenzyme patient samples. <h3>Results</h3> identified...
Polyadenylation has well characterised roles in RNA turnover and translation a variety of biological systems. While polyadenylation on mitochondrial transcripts been suggested to be two-step process required complete translational stop codons, its involvement is less understood. We studied knockdown knockout models the poly(A) polymerase (MTPAP) Drosophila melanogaster demonstrate that mRNAs exclusively performed by MTPAP. Further, our results show does not regulate mRNA stability but...
The RNA helicase SUV3 and the polynucleotide phosphorylase PNPase are involved in degradation of mitochondrial mRNAs but their roles vivo not fully understood. Additionally, upstream processes, such as transcript maturation, have been linked to some these factors, suggesting either dual or tightly interconnected mechanisms metabolism. To get a better understanding turn-over RNAs vivo, we manipulated mRNA degrading complex Drosophila melanogaster models studied molecular consequences....
Abstract The investigation of genetic forms juvenile neurodegeneration could shed light on the causative mechanisms neuronal loss. Schinzel-Giedion syndrome (SGS) is a fatal developmental caused by mutations in SETBP1 gene, inducing accumulation its protein product. SGS features multi-organ involvement with severe intellectual and physical deficits due, at least part, to early neurodegeneration. Here we introduce human model that displays disease-relevant phenotypes. We show neural...
Neurodegenerative disorders are an increasingly common and irreversible burden on society, often affecting the aging population, but their etiology disease mechanisms poorly understood. Studying monogenic neurodegenerative diseases with known genetic cause provides opportunity to understand cellular also affected in more complex disorders. We recently reported that loss-of-function mutations autophagy adaptor protein SQSTM1/p62 lead a slowly progressive presenting childhood. To further...
In all biological systems, RNAs are associated with RNA-binding proteins (RBPs), forming complexes that control gene regulatory mechanisms, from RNA synthesis to decay. mammalian mitochondria, post-transcriptional regulation of expression is conducted by mitochondrial RBPs (mt-RBPs) at various stages mt-RNA metabolism, including polycistronic transcript production, its processing into individual transcripts, modifications, stability, translation and degradation. To date, only a handful...
Huntington's disease (HD) causes selective degeneration of striatal and cortical neurons, resulting in cell mosaicism coexisting still functional dysfunctional cells. The impact non-cell autonomous mechanisms between these cellular states is poorly understood. Here we generated telencephalic organoids with healthy or HD cells, grown separately as mosaics the two genotypes. Single-cell RNA sequencing revealed neurodevelopmental abnormalities ventral fate acquisition organoids, confirmed by...
Thioredoxin-interacting protein (TXNIP) is an α-arrestin that can bind to and inhibit the antioxidant thioredoxin (TXN). TXNIP expression induced by glucose promotes β-cell apoptosis in pancreas, deletion of its gene mouse models protects against diabetes. currently studied as a potential new target for antidiabetic drug therapy. In this study, we describe family with mutation leading nondetectable protein. Symptoms affected members include lactic acidosis low serum methionine levels. Using...
Here, we present a revised protocol to derive neuroepithelial stem (NES) cells from human induced pluripotent cells. NES can be further differentiated into culture of neurons (90%) and glia (10%). We describe how maintain in differentiate them. In addition, show the potential use study role reactive oxygen species neuronal differentiation guideline for cell transfection. For complete details on execution this protocol, please refer Calvo-Garrido et al. (2019); Falk (2012).
Abstract Background Mutations in mitochondrial aminoacyl tRNA synthetases form a subgroup of disorders often only perturbing brain function by affecting translation. Here we report two siblings with disease, due to compound heterozygous mutations the tryptophanyl‐tRNA synthetase ( WARS2 ) gene, presenting severe neurological symptoms but normal skeletal muscle biopsies and cultured skin fibroblasts. Methods Whole exome sequencing on genomic DNA samples from both subjects their parents...
Mutations in structural subunits and assembly factors of complex I the oxidative phosphorylation system constitute most common cause mitochondrial respiratory chain defects. Such mutations can present a wide range clinical manifestations, varying from mild deficiencies to severe, lethal disorders. We describe patient presenting intrauterine growth restriction anemia, which displayed postpartum hypertrophic cardiomyopathy, lactic acidosis, encephalopathy, severe defect with fatal outcome....