A5012729392- Parkinson's Disease Mechanisms and Treatments
- Microtubule and mitosis dynamics
- Neurological disorders and treatments
- Alzheimer's disease research and treatments
- Histone Deacetylase Inhibitors Research
- Mitochondrial Function and Pathology
- Nerve injury and regeneration
- Cancer Treatment and Pharmacology
- Synthesis and biological activity
- Genetic Neurodegenerative Diseases
- Retinoids in leukemia and cellular processes
- Neuroscience and Neuropharmacology Research
- Click Chemistry and Applications
- 14-3-3 protein interactions
- Cellular transport and secretion
- Paraquat toxicity studies and treatments
- Nuclear Receptors and Signaling
- Nitric Oxide and Endothelin Effects
- Botulinum Toxin and Related Neurological Disorders
- Genetics and Neurodevelopmental Disorders
- Ubiquitin and proteasome pathways
- Receptor Mechanisms and Signaling
- Autophagy in Disease and Therapy
- Biochemical effects in animals
- Synthetic Organic Chemistry Methods
University of Milan
2015-2024
Institute of Biosciences and Bioresources
2022
University of Birmingham
2013
Fondazione IRCCS Istituto Nazionale dei Tumori
2008-2009
Indena (Italy)
2008
Mesenchymal stromal cells may represent an ideal candidate to deliver anti-cancer drugs. In a previous study, we demonstrated that exposure of mouse bone marrow derived Doxorubicin led them acquire anti-proliferative potential towards co-cultured haematopoietic stem (HSCs). We thus hypothesized whether freshly isolated human (hMSCs) and mature murine (SR4987 line) primed in vitro with drugs then localized near cancer cells, could inhibit proliferation.Paclitaxel (PTX) was used prime culture...
The role of microtubule (MT) dysfunction in Parkinson's disease is emerging. It still unknown whether it a cause or consequence neurodegeneration. Our objective was to assess alterations MT stability precede follow axonal transport impairment and neurite degeneration experimental parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) C57Bl mice. MPTP time- dose-dependent increase fibres with altered mitochondria distribution, early changes cytoskeletal proteins...
α-Synuclein is a presynaptic protein associated to Parkinson's disease, which unstructured when free in the cytoplasm and adopts α helical conformation bound vesicles. After decades of intense studies, physiology still difficult clear up due its interaction with multiple partners involvement pletora neuronal functions. Here, we looked at remarkably neglected interplay between microtubules, potentially impacts on synaptic functionality. In order identify mechanisms underlying these actions,...
Abstract Mutations in GBA1 , the gene encoding lysosomal enzyme β-glucocerebrosidase (GCase), which cause Gaucher’s disease, are most frequent genetic risk factor for Parkinson’s disease (PD). Here, we employ global proteomic and single-cell genomic approaches stable cell lines as well induced pluripotent stem (iPSC)-derived neurons midbrain organoids to dissect mechanisms underlying GCase-related neurodegeneration. We demonstrate that GCase can be imported from cytosol into mitochondria via...
Abstract Highly specialized microtubules in neurons are crucial to both health and disease of the nervous system, their properties strictly regulated by different post-translational modifications, including α-Tubulin acetylation. An imbalance levels acetylated has been reported experimental models Parkinson’s (PD) whereas pharmacological or genetic modulation that leads increased successfully rescues axonal transport defects inhibits α-Synuclein aggregation. However, role acetylation human...
Abstract Parkinson’s disease is characterized by a progressive accumulation of alpha-Synuclein (αSyn) neuronal inclusions called Lewy bodies in the nervous system. can arise from cell-to-cell propagation αSyn, which occur via sequential steps secretion and uptake. Here, fusing removable short signal peptide to N-terminus we developed novel mouse model with enhanced αSyn transmission. Expression secreted brain was under control hybrid promoter combination adeno-associated virus serotype 9...
J. Neurochem. (2010) 115 , 247–258. Abstract Dysfunction of the microtubule (MT) system is an emerging theme in pathogenesis Parkinson’s disease. This study was designed to investigate putative role MT dysfunction dopaminergic neuron death induced by neurotoxin 1‐methyl‐4‐phenylpiridinium (MPP + ). In nerve growth factor‐differentiated PC12 cells, we have analyzed post‐translational modifications tubulin known be associated with differently dynamic MTs and show that MPP causes a selective...
Hereditary spastic paraplegia (HSP) is characterized by weakness and spasticity of the lower limbs, owing to degeneration corticospinal axons. The most common form due heterozygous mutations in SPG4 gene, encoding spastin, a microtubule (MT)-severing protein. Here, we show that neurite growth immortalized primary neurons responds pleiotropic ways changes spastin levels. Spastin depletion alters development hippocampal leading abnormal neuron morphology, dystrophic neurites, axonal defects....
Parkinson's disease (PD) stands as the most prevalent degenerative movement disorder, marked by degeneration of dopaminergic neurons in substantia nigra midbrain. In this study, we conducted a transcriptome analysis utilizing post mortem mRNA extracted from both PD patients and healthy control (CTRL) individuals. Specifically, acquired eight samples individuals with six CTRL individuals, no discernible pathology detected latter group. RNA sequencing was using TapeStation 4200 system Agilent...
Abstract A variety of cellular processes, including vesicle clustering in the presynaptic compartment, are impaired Parkinson’s disease and have been closely associated with α-synuclein oligomerization. Emerging evidence proves existence α-synuclein-related pathology peripheral nervous system, even though presence oligomers situ living patients remains poorly investigated. In this case-control study, we show previously undetected within synaptic terminals autonomic fibres skin biopsies by...
Dysfunction of the microtubule system is emerging as a contributing factor in number neurodegenerative diseases. Looking for potential role played by cytoskeleton neuron degeneration underlying Parkinson's disease (PD), we investigate influence parkinsonism producing neurotoxin 1-methyl-4-phenylpyridinium (MPP+) on dynamics. We find that it acts strong catastrophe promoter causing decrease average length microtubules assembled from purified tubulin. also reduces nucleated centrosomes....
Data from both toxin-based and gene-based models suggest that dysfunction of the microtubule system contributes to pathogenesis Parkinson's disease, even if, at present, no evidence alterations microtubules in vivo or patients is available. Here we analyze cytoskeleton organization primary fibroblasts deriving with idiopathic genetic focusing on mutations parkin leucine-rich repeat kinase 2. Our analyses reveal likely pathology affects cytoskeletal stability, without any activation autophagy...
Although loss-of-function mutations in the PARK2 gene, gene that encodes protein parkin, cause autosomal recessive juvenile parkinsonism, responsible molecular mechanisms remain unclear. Evidence suggests a loss of parkin dysregulates excitatory synapses. Here we show interacts with kainate receptor (KAR) GluK2 subunit and regulates KAR function. Loss function primary cultured neurons causes to accumulate plasma membrane, potentiates currents increases KAR-dependent excitotoxicity....
Striatin (Strn) is a scaffold protein expressed in cardiomyocytes (CMs) and alteration of its expression are described various cardiac diseases. However, the underlying pathogenicity have been poorly investigated.
Poly-ADP-ribosylation (PARylation), catalyzed by the enzyme PARP1, involves addition of poly-ADP-ribose polymers (PAR) and has been associated with α-synuclein aggregation in Parkinson′s disease (PD) models. This study aimed to unravel role PARylation neuronal cell death complex environment post-mortem human PD brains. Using high-resolution imaging 3D reconstruction analysis, we observed that PAR accumulate cytoplasm regions affected pathology, preceding formation oligomers. Additionally,...
Abstract Variations in the POLG1 gene encoding catalytic subunit of mitochondrial DNA polymerase gamma, have recently been associated with Parkinson’s disease (PD), especially patients diagnosed progressive external ophthalmoplegia (PEO). However, majority studies reporting this association mainly focused on genetic identification variation PD patient primary cells, and determination copy number, providing little information about cellular alterations existing brain particular dopaminergic...