A5050171363- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
- Neurological Disease Mechanisms and Treatments
- Circular RNAs in diseases
- RNA modifications and cancer
- Neurotransmitter Receptor Influence on Behavior
- Alzheimer's disease research and treatments
- Plant-based Medicinal Research
- RNA Research and Splicing
- Cancer-related gene regulation
- Cell death mechanisms and regulation
- Nuclear Receptors and Signaling
- Ferroptosis and cancer prognosis
- Neurological diseases and metabolism
- Forensic Toxicology and Drug Analysis
- Neurogenesis and neuroplasticity mechanisms
- Amyotrophic Lateral Sclerosis Research
- Traditional Chinese Medicine Analysis
- interferon and immune responses
- Wnt/β-catenin signaling in development and cancer
- Molecular Biology Techniques and Applications
- Parkinson's Disease Mechanisms and Treatments
- FOXO transcription factor regulation
Sanofi (United States)
2021-2025
Framingham State University
2021
Sanofi (Mexico)
2021
Bambino Gesù Children's Hospital
2021
Istituti di Ricovero e Cura a Carattere Scientifico
2021
Albert Einstein College of Medicine
2010-2020
Ospedale G.B. Morgagni - L.Pierantoni
2018-2020
John F. Kennedy Medical Center
2017-2018
Hackensack Meridian Health
2018
John F. Kennedy Center for the Performing Arts
2016
In animals, sporadic injections of the mitochondrial toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) selectively damage dopaminergic neurons but do not fully reproduce features human Parkinson's disease. We have now developed a mouse disease model that is based on continuous MPTP administration with an osmotic minipump and mimics many Although both led to severe striatal dopamine depletion nigral cell loss, we find only produced progressive behavioral changes triggered formation...
Iron dysregulation has been implicated in multiple neurodegenerative diseases, including Parkinson's disease (PD). Iron-loaded microglia are frequently found affected brain regions, but how iron accumulation influences physiology and contributes to neurodegeneration is poorly understood. Here we show that human induced pluripotent stem cell-derived grown a tri-culture system highly responsive susceptible ferroptosis, an iron-dependent form of cell death. Furthermore, overload causes marked...
The mammalian target of rapamycin (mTOR) is a key regulator cell growth, autophagy, translation, and survival. Dysregulation mTOR signaling associated with cancer, diabetes, autism. However, role for in neuronal death not well delineated. Here we show that global ischemia triggers transient increase phosphorylation at S2448, whereas decreasing p-mTOR functional activity selectively vulnerable hippocampal CA1 neurons. decrease coincides an biochemical markers pS317-ULK-1, pS14-Beclin-1,...
Receptor interacting protein kinase 1 (RIPK1) mediates cell death and inflammatory signaling is increased in multiple sclerosis (MS) brain samples. Here, we investigate the role of glial RIPK1 activity mediating MS pathogenesis. We demonstrate levels correlate with disease progression. find microglia are susceptible to RIPK1-mediated identify an gene signature that may contribute neuroinflammatory milieu patients. uncover a distinct for astrocytes regulating absence confirm...
Expression of Dickkopf-1 (Dkk-1), a secreted protein that negatively modulates the Wnt pathway, was induced in hippocampus gerbils and rats subjected to transient global cerebral ischemia as well cultured cortical neurons challenged with an excitotoxic pulse. In ischemic animals, temporal regional pattern Dkk-1 expression correlated profile neuronal death, assessed by Nissl staining immunostaining adjacent hippocampal sections. Treatment animals either antisense oligonucleotides or lithium...
Repressor Element-1 (RE1) Silencing Transcription Factor/Neuron-Restrictive Silencer Factor (REST/NRSF) is a gene-silencing factor that widely expressed during embryogenesis and plays strategic role in neuronal differentiation. Recent studies indicate REST can be activated differentiated neurons critical window of time postnatal development adult response to insults such as seizures ischemia. However, the mechanism by which regulated yet unknown. Here, we show controlled at level protein...
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron loss. Microglia and astrocyte-driven neuroinflammation prominent in ALS, but the cell state dynamics pathways driving remain unclear. We performed single-nucleus RNA sequencing of ALS spinal cords identified altered glial states, including increased expression inflammatory activation markers. Many these signals converged on inflammation death regulator receptor-interacting protein...
Transient global ischemia arising in human due to cardiac arrest causes selective, delayed neuronal death hippocampal CA1 and cognitive impairment. Growth DNA-damage-inducible protein 45 beta (Gadd45b) is a wellknown molecule both DNA damage-related pathogenesis therapies. Emerging evidence suggests that Gadd45b an anti-apoptotic factor nonneuronal cells intrinsic neuroprotective neurons. However, the mechanism of pathway not fully examined neurodegeneration associated with ischemia. Rats...
Abstract Background During the first SARS-CoV-2 pandemic phase, sudden closure of schools was one main measures to minimize spread virus. In second several safety procedures were implemented avoid school closure. To evaluate if is a safe place, students and staff two complexes Rome monitored efficacy prevention inside buildings. Methods Oral secretions specimens collected from 1262 subjects for total 3431 samples, over 3 months period. Detection Coronavirus performed by real-time PCR. Target...
Abstract Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that causes motor neuron loss in the brain and spinal cord. Neuroinflammation driven by activated microglia astrocytes prominent ALS, but an understanding of cell state dynamics which pathways contribute to remains unclear. Single nucleus RNA sequencing ALS cords demonstrated striking changes glial states, including increased expression inflammatory activation markers. Many these signals converged on...
Transient global ischemia in rodents induces delayed death of hippocampal CA1 neurons, as well some hilar neurons the dentate gyrus, medium aspiny striatum, pyramidal neocortical layers II, V and VI, Purkinje cerebellum. In contrast to focal that mimics regional stroke humans, this model brain injury occurs after human cardiac arrest. Early events include caspase activation, cleavage anti-death Bcl-2 family proteins large mitochondrial channel activity. Genetically engineered mice provide...
Abstract Iron dysregulation has been implicated in multiple neurodegenerative diseases, including Parkinson’s Disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Multiple (MS). One prominent feature of affected brain regions are iron-loaded microglia, but how iron overload influences microglia physiology disease response is poorly understood. Here we show that highly susceptible to ferroptosis, an iron-dependent form cell death. In a tri-culture human iPSC-derived neurons, astrocytes,...
Transient global ischemia arising as a consequence of cardiac arrest in humans causes selective, delayed death hippocampal CA1 pyramidal neurons and cognitive impairment. Effective treatments to ameliorate the neurodegeneration dysfunction associated with are an unmet need. Emerging evidence points widespread role for microRNAs (miRNAs) key modulators target gene expression neurons. Accordingly, dysregulation miRNAs implicated pathophysiology neurodegenerative disease neurological disorders....
Global cerebral ischemia occurs when blood flow to the entire brain is transiently blocked, which results in delayed neurologic deficits. Here, we present a protocol for performing four-vessel occlusion rat model study neurodegeneration and cognitive deficits associated with global ischemia. We describe steps carrying out vertebral common carotid artery enables sufficient blockage of flow. then detail expected outcomes using histology assays behavioral tests. For complete details on use...
Presenilins (PS1 and PS2) are transmembrane aspartyl proteases active catalytic subunits of gamma-secretase. Autosomal dominant mutations in genes encoding PS1 PS2 cause a familial form Alzheimer's disease (FAD) humans. Gamma-secretase is multi-subunit protease complex that cleaves integral membrane proteins including amyloid precursor protein. Neuronal expression peaks during the critical period, time early postnatal development characterized by heightened sensitivity to bidirectional forms...
The mammalian genome pervasively transcribes a variety of functional noncoding transcripts, including the recently discovered long RNAs (lncRNAs). LncRNAs play major roles in regulating gene expression mammals, but their and functions post-stroke brain remain largely unknown. Using mouse model transient focal ischemia, we applied RNA-sequencing to evaluate for first time unbiased, genome-wide lncRNAs as function reperfusion cerebral cortex. A 1h middle artery occlusion was conducted adult...