A5056224918- Amyotrophic Lateral Sclerosis Research
- Advanced Radiotherapy Techniques
- Nerve injury and regeneration
- Neurogenetic and Muscular Disorders Research
- Neuroscience and Neural Engineering
- Cellular transport and secretion
- Microtubule and mitosis dynamics
- Sarcoma Diagnosis and Treatment
- RNA Research and Splicing
- Neuroscience and Neuropharmacology Research
- RNA Interference and Gene Delivery
- 3D Printing in Biomedical Research
- Signaling Pathways in Disease
- Mitochondrial Function and Pathology
- Neurogenesis and neuroplasticity mechanisms
- Hereditary Neurological Disorders
- Axon Guidance and Neuronal Signaling
- Bacillus and Francisella bacterial research
- Rabies epidemiology and control
- Lipid Membrane Structure and Behavior
- RNA modifications and cancer
- MicroRNA in disease regulation
- Virology and Viral Diseases
- Genetic Neurodegenerative Diseases
- Alzheimer's disease research and treatments
Tel Aviv University
2015-2024
University of California, San Diego
2020
Arthur M. Sackler Gallery
2019
University of Pennsylvania
2008-2013
Weizmann Institute of Science
2003-2006
Ben-Gurion University of the Negev
2004
Mislocalization of the predominantly nuclear RNA/DNA binding protein, TDP-43, occurs in motor neurons ~95% amyotrophic lateral sclerosis (ALS) patients, but contribution axonal TDP-43 to this neurodegenerative disease is unclear. Here, we show accumulation intra-muscular nerves from ALS patients and axons human iPSC-derived patient, as well neuromuscular junctions (NMJs) a mislocalization mouse model. In axons, hyper-phosphorylated promotes G3BP1-positive ribonucleoprotein (RNP) condensate...
Brain-derived neurotrophic factor (BDNF) and its receptors tropomyosin kinase receptor B (TrkB) the p75 neurotrophin (p75) are primary regulators of dendritic growth in CNS. After being bound by BDNF, TrkB endocytosed into endosomes continue signaling within cell soma, dendrites, axons. We studied functional role BDNF axonal cortical neurons derived from different transgenic mice using compartmentalized cultures microfluidic devices. found that increased neuronal body a cAMP response...
Retrograde axonal transport of cellular signals driven by dynein is vital for neuronal survival. Mouse models with defects in the retrograde machinery, including Loa mouse (point mutation dynein) and Tg dynamitin (overexpression dynamitin), exhibit mild neurodegenerative disease. Transport have also been observed more rapidly progressive neurodegeneration, such as that SOD1 G93A transgenic model familial amyotrophic lateral sclerosis (ALS). Here, we test hypothesis alterations signaling lead...
Bidirectional molecular communication between the motoneuron and muscle is vital for neuromuscular junction (NMJ) formation maintenance. The mechanisms underlying such are of keen interest may provide new targets intervention in motor neuron disease. Here we developed a microfluidic platform with (MN) cell bodies on one side cells other, connected via axons extending through microgrooves to form functional NMJs. Using this system, were able differentiate proximal distal effects oxidative...
Rabies virus (RABV) is a neurotropic that depends on long distance axonal transport in order to reach the central nervous system (CNS). The strategy RABV uses hijack cellular machinery still not clear. It thought interacts with membrane receptors internalize and exploit endosomal trafficking pathway, yet this has never been demonstrated directly. p75 Nerve Growth Factor (NGF) receptor (p75NTR) binds Glycoprotein (RABV-G) high affinity. However, as p75NTR essential for infection, specific...
Amyotrophic lateral sclerosis (ALS) is a multifactorial lethal motor neuron disease with no known treatment. Although the basic mechanism of its degenerative pathogenesis remains poorly understood, subcellular spatial alteration in RNA metabolism thought to play key role. The nature these RNAs elusive, and comprehensive characterization axonal involved maintaining neuronal health has yet be described. Here, using cultured spinal cord (SC) neurons grown compartmented platform followed by...
COPII and COPI mediate the formation of membrane vesicles translocating in opposite directions within secretory pathway. Live-cell electron microscopy revealed a novel mode function for during cargo export from ER. is recruited to membranes defining boundary between ER exit sites, facilitating selective concentration. Using direct observation living cells, we monitored selection processes, accumulation, fission COPII-free ERES membranes. CRISPR/Cas12a tagging, RUSH system, pharmaceutical...
Abstract Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease affecting both the upper and lower motor neurons (MNs), with no effective treatment currently available. Early pathological events in ALS include perturbations axonal transport (AT), formation of toxic protein aggregates Neuromuscular Junction (NMJ) disruption, which all lead to degeneration neuron death. Pridopidine small molecule that has been clinically developed for Huntington disease. Here we tested...
Protein sulfonation on serine and threonine residues is described for the first time. This post-translational modification shown to occur in proteins isolated from organisms representing a broad span of eukaryote evolution, including invertebrate mollusk Lymnaea stagnalis, unicellular malaria parasite Plasmodium falciparum, humans. Detection structural characterization this novel was carried out using liquid chromatography coupled electrospray tandem mass spectrometry neuronal intermediate...
Adeno-associated virus (AAV) vectors can move along axonal pathways after brain injection, resulting in transduction of distal regions. This enhance the spread therapeutic gene transfer and improve treatment neurogenetic disorders that require global correction. To better understand underlying cellular mechanisms drive AAV trafficking neurons, we investigated transport dye-conjugated AAV9, utilizing microfluidic primary neuron cultures isolate cell bodies from axon termini permit independent...
ABSTRACT ASR1 is a plant‐specific, highly charged, low molecular weight polypeptide. Purified was shown to posses sequence specific Zn 2+ ‐dependent DNA binding activity (Kalifa et al . Biochemical Journal 381, 373–378, 2004). Steady‐state levels of tomato Asr1 mRNA and protein are transiently increased following exposure plants polyethylene glycol, NaCl or abscisic acid. The biological role could not be deduced from analyses homologies. Tobacco over‐expressing have decreased rate water loss...
Axon degeneration and disruption of neuromuscular junctions (NMJs) are key events in amyotrophic lateral sclerosis (ALS) pathology. Although the disease9s etiology is not fully understood, it thought to involve a non–cell-autonomous mechanism alterations RNA metabolism. Here, we identified reduced levels miR126-5p presymptomatic ALS male mice models, an increase its targets: axon destabilizing Type 3 Semaphorins their coreceptor Neuropilins. Using compartmentalized <i>in vitro</i>...
Exercise prevents cancer incidence and recurrence, yet the underlying mechanism behind this relationship remains mostly unknown. Here we report that exercise induces metabolic reprogramming of internal organs increases nutrient demand protects against metastatic colonization by limiting availability to tumor, generating an exercise-induced shield. Proteomic ex vivo capacity analyses murine revealed catabolic processes, glucose uptake, mitochondrial activity, GLUT expression. analysis...
Rabies virus (RABV) spread is widely accepted to occur only by retrograde axonal transport. However, examples of anterograde RABV in peripheral neurons such as dorsal root ganglion (DRG) indicated a possible bidirectional transport an uncharacterized mechanism. Here, we analyzed the fluorescence-labeled DRG live-cell microscopy. Both entry-related after infection at axon endings and postreplicative newly formed were visualized compartmentalized neuron cultures. Whereas 1.5 μm/s occurred...
Local protein synthesis in neuronal axons plays an important role essential spatiotemporal signaling processes; however, the molecular basis for post-transcriptional regulation controlling this process is still not fully understood. Here we studied axonal mechanisms underlying transport and localization of microRNA (miRNA) RNAi machinery along axon. We first identified miRNAs, Dicer, Argonaute-2 (Ago2) motor neuron (MN) axons. then demonstrated that mitochondria associate with miR-124...