A5044322212- Lysosomal Storage Disorders Research
- Neurogenesis and neuroplasticity mechanisms
- Cellular transport and secretion
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Hedgehog Signaling Pathway Studies
- Nerve injury and regeneration
- Epigenetics and DNA Methylation
- Protein Hydrolysis and Bioactive Peptides
- Sulfur Compounds in Biology
- Functional Brain Connectivity Studies
- Genetics, Aging, and Longevity in Model Organisms
- Neuroscience and Neuropharmacology Research
- Neonatal and fetal brain pathology
- Antimicrobial Peptides and Activities
- TGF-β signaling in diseases
- Regulation of Appetite and Obesity
- Eating Disorders and Behaviors
- Developmental Biology and Gene Regulation
- Sleep and Wakefulness Research
- Neurogenetic and Muscular Disorders Research
- Lipid Membrane Structure and Behavior
- Biological Research and Disease Studies
- Genomics, phytochemicals, and oxidative stress
- Genetic Neurodegenerative Diseases
Sapienza University of Rome
2015-2024
Fondazione Santa Lucia
2023-2024
Istituto Pasteur
2004-2013
The Niemann-Pick type C1 (NPC1) disease is a neurodegenerative lysosomal storage disorder due to mutations in the NPC1 gene, encoding transmembrane protein related Sonic hedgehog (Shh) receptor, Patched, and involved intracellular trafficking of cholesterol. We have recently found that proliferation cerebellar granule neuron precursors significantly reduced Npc1−/− mice downregulation Shh expression. This finding prompted us analyze formation primary cilium, non-motile organelle specialized...
During the early development of cerebellum, a burst granule cell progenitor (GCP) proliferation occurs in outer external layer (EGL), which is sustained mainly by Purkinje cell-derived Sonic Hedgehog (Shh). Shh response interrupted once GCPs move into inner EGL, where progenitors withdraw and start differentiating migrating toward internal (IGL). Failure to interrupt signals results uncoordinated differentiation eventually leads malignancy (i.e., medulloblastoma). The inhibitory mechanisms...
Niemann-Pick type C1 (NPC1) disease is a lysosomal storage disorder caused by defective intracellular trafficking of exogenous cholesterol. Purkinje cell (PC) degeneration the main sign cerebellar dysfunction in both NPC1 patients and animal models. It has been recently shown that significant decrease Sonic hedgehog (Shh) expression reduces proliferative potential granule neuron precursors developing cerebellum Npc1 −/− mice. Pursuing hypothesis this developmental defect translates into...
Discovered in pig brains 1982, the brain-derived neurotrophic factor (BDNF) is one of most studied and characterized neurotrophins central nervous system. In recent years, BDNF has received considerable attention for its importance development maintenance normal brain function. This because plays an important role crucial functions system, such as survival, differentiation, maturation neurons glial cells well actions neuroprotection adverse conditions, glutamatergic overstimulation, cerebral...
In this study we show that postnatal development of cerebellar granule neurons (GNs) is defective in Npc1(-/-) mice. Compared to age-matched wild-type littermates, there an accelerated disappearance the external layer (EGL) these This due a premature exit from cell cycle GN precursors residing at level EGL. As consequence, size lobules mice displays 20%-25% reduction compared detectable post-natal day 28 (PN28), when completed while signs neuronal atrophy are not yet apparent. Based on...
Niemann-Pick type C (NPC) disease is a lysosomal storage disorder characterized by the occurrence of visceral and neurological symptoms. At present, molecular mechanisms causing neurodegeneration in this are unknown. Here we report altered expression and/or mislocalization TAR-DNA binding protein 43 (TDP-43) both NPC mouse human neuronal model disease. We also neuropathologic study patient's brain, showing that while TDP-43 below immunohistochemical detection nuclei cerebellar Purkinje...
Reactive and proactive controls of actions are cognitive abilities that allow one to deal with a continuously changing environment by adjusting already programmed actions. They also set forthcoming evaluating the outcome previous ones. Earlier studies highlighted sex-related differences in strategies pattern brain activation during tasks involving reactive control. To further identify sex-dependent characteristics control actions, this study, we have assessed whether/how performance...
Niemann-Pick C1 (NPC) disease, also known as "juvenile Alzheimer's disease", is a disease in which alterations intracellular cholesterol trafficking occur. The contribution of various CNS cell types to the neurodegeneration has been much intere
The inability to learn an adaptive coping strategy in a novel stressful condition leads dysfunctional stress coping, marker of mental disturbances. This study tested the involvement dorsal striatal dopamine receptors with Forced Swim test fostered by previous experience reduced food availability. Adult male mice were submitted temporary (12 days) reduction availability [food-restricted (FR)] or continuously free-fed (FF). Different groups FF and FR used evaluate: (1) mRNA levels two isoforms...
The lysosomal storage disorder, Niemann Pick type C1 (NPC1), presents a variable phenotype including neurovisceral and neurological symptoms. 2-Hydroxypropyl-ß-cyclodextrin (HPßCD)-based therapies are presently the most promising route of intervention. While severe cerebellar dysfunction remains main disabling feature NPC1, sensory functions auditory olfactory ones also affected. Morphological functional anomalies Npc1 −/− mouse retina have been observed, although integrity visual pathway...
Alzheimer's Disease (AD) represents the most frequent type of dementia in elderly people. There are two major forms disease: sporadic (SAD) - whose causes not completely understood and familial (FAD) with clear autosomal dominant inheritance. The main hallmarks AD extracellular deposits amyloid-beta (Ab) peptide intracellular hyperphosphorylated form tau protein (P-tau). An ever-growing body research supports infectious hypothesis AD. Indeed, it has been documented that some pathogens, such...
In fertilized mouse eggs, de novo transcription of embryonic genes is first observed during the S phase one-cell stage. This transcription, however, mostly limited to male pronucleus and possibly uncoupled from translation, making functional meaning obscure. We found that embryos respond osmotic shock in vitro isolation with migration HSF1, canonical stress activator mammalian heat genes, pronuclei by transient hsp70.1, but not hsp70.3 hsp90, genes. Isolated growing dictyate oocytes also...
Abstract Proteins belonging to the TGFβ‐stimulated clone 22 domain (TSC22D) family display a repertoire of activities, regulating cell proliferation and differentiation. The tumor suppressor activity first identified member family, TSC22D1 (formerly named TSC‐22), has been extensively studied, but afterward longer isoform encoded by same gene turned out play an opposite role. We have previously characterized role TSC22D4 in differentiation using granule neurons (GNs) isolated from mouse...
Physical distancing due to the COVID-19 Pandemic has limited opportunities for family members, friends, and significant others show physical affection (i.e., hugs, kisses, caresses, holding hands) during social interactions. The present study investigated effects of positive touch psychological distress in 991 Italian participants (