A5043533177- Glycogen Storage Diseases and Myoclonus
- Hereditary Neurological Disorders
- Genetics and Neurodevelopmental Disorders
- Ubiquitin and proteasome pathways
- Amyotrophic Lateral Sclerosis Research
- Cellular Mechanics and Interactions
- Neurogenetic and Muscular Disorders Research
- Signaling Pathways in Disease
- RNA regulation and disease
- Lysosomal Storage Disorders Research
- Cell death mechanisms and regulation
- Genetic Neurodegenerative Diseases
- RNA Interference and Gene Delivery
- Histone Deacetylase Inhibitors Research
- Mitochondrial Function and Pathology
- Autophagy in Disease and Therapy
- Pancreatic function and diabetes
- Genetic Syndromes and Imprinting
- Mesenchymal stem cell research
- Protein Tyrosine Phosphatases
- Developmental Biology and Gene Regulation
- Endoplasmic Reticulum Stress and Disease
- RNA Research and Splicing
- Nanoparticle-Based Drug Delivery
- Autoimmune Neurological Disorders and Treatments
Tel Aviv University
2015-2025
Alzheimer's Association of Israel
2010
Medical Research Council
1997-2000
University College London
1996-1999
MRC Laboratory for Molecular Cell Biology
1996-1998
In the presence of cycloheximide (CHX) to inhibit protein synthesis, a high concentration staurosporine (STS) induces almost all cells in explant cultures 8/8 types newborn mouse organs and 3/3 adult die with characteristic features apoptosis. Eggs blastomeres also this way when treated STS CHX, although they are less sensitive treatment than trophectoderm or inner cell mass whose sensitivity resembles that other developing cells. Human red blood exceptional being completely resistant CHX....
In the accompanying paper by Weil et al. (1996) we show that staurosporine (STS), in presence of cycloheximide (CHX) to inhibit protein synthesis, induces apoptotic cell death a large variety nucleated mammalian types, suggesting all cells constitutively express proteins required undergo programmed (PCD). The reliability conclusion depends on evidence STS-induced, and (STS + CHS)-induced, deaths are bona fide examples PCD. There is rapidly accumulating some members Ced-3/Interleukin-1 beta...
The selective degeneration of an axon, without the death parent neuron, can occur in response to injury, a variety metabolic, toxic, and inflammatory disorders, during normal development. Recent evidence suggests that some forms axon involve active regulated program self-destruction rather than passive “wasting away” this respect others resemble apoptosis. Here we investigate whether depends on molecular machinery mediates apoptosis, namely, caspase family cysteine proteases. We focus two...
We show that mouse sperm die spontaneously within 1-2 days in culture and treatment with either staurosporine (STS) cycloheximide (CHX) or a peptide caspase inhibitor does not accelerate delay the cell death. Chicken erythrocytes, by contrast, are induced to serum deprivation STS CHX, embryonic erythrocytes more sensitive than adult both treatments. Although these erythrocyte deaths display number of features characteristic apoptosis, they blocked, even delayed, inhibitors, most cells...
The axonal transport of vesicles promotes microtubule acetylation across species.
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>...
Deficiency in the IKAP/Elp1 protein leads to recessive sensory autosomal congenital neuropathy which is called familial dysautonomia (FD). This was originally identified as a role player transcriptional elongation being subunit of RNAPII Elongator multi-protein complex. Subsequently, shown play various functions cytoplasm. Here, we describe experiments performed with downregulated cell lines and FD-derived cells tissues. Immunostaining cytoskeleton component α-tubulin revealed...
A splicing mutation in the ikbkap gene causes Familial Dysautonomia (FD), affecting IKAP protein expression levels and proper development function of peripheral nervous system (PNS). Here we attempted to elucidate role PNS chick embryo found that is required for axonal outgrowth, branching, target innervation. Moreover, demonstrate colocalizes with activated JNK (pJNK), dynein, β-tubulin at axon terminals dorsal root ganglia (DRG) neurons, may be involved transport specific derived signals...
Polymorphism in TCF7L2, a component of the canonical Wnt signaling pathway, has strong association with β-cell dysfunction and type 2 diabetes through mechanism that yet to be defined. β-Cells rely on cells their microenvironment, including pericytes, for proper function. Here, we show Tcf7l2 activity pancreatic pericytes is required Transgenic mice which was selectively inactivated exhibited impaired glucose tolerance due compromised function glucose-stimulated insulin secretion....
Adult polyglucosan body disease (APBD) is a late-onset caused by intracellular accumulation of bodies, formed due to glycogen-branching enzyme (GBE) deficiency. To find treatment for APBD, we screened 1,700 FDA-approved compounds in fibroblasts derived from APBD-modeling GBE1-knockin mice. Capitalizing on fluorescent periodic acid-Schiff reagent, which interacts with polyglucosans the cell, this screen discovered that flavoring agent guaiacol can lower polyglucosans, result also confirmed...
The pro-inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β) are expressed simultaneously have tumor-promoting roles in breast cancer. In parallel, mesenchymal stem cells (MSCs) undergo conversion at the site to cancer-associated fibroblasts (CAFs), which generally connected enhanced progression. Here, we determined impact of consistent inflammatory stimulation on stromal cell plasticity. MSCs that were persistently stimulated by TNFα + IL-1β (generally 14–18...
Article6 September 2021Open Access Source DataTransparent process Alleviation of a polyglucosan storage disorder by enhancement autophagic glycogen catabolism Or Kakhlon Corresponding Author [email protected] orcid.org/0000-0001-7435-6454 Department Neurology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel Search for more papers this author Hilla Vaknin orcid.org/0000-0001-9101-1423 Laboratory Neurodegenerative Diseases and Personalized Medicine, The Cell Screening Facility...
The protein p27Kip1 plays roles that extend beyond cell-cycle regulation during cerebral cortex development, such as the of neuronal migration and neurite branching via signaling pathways converge on actin microtubule cytoskeletons. Microtubule-dependent transport is essential for maturation neurons establishment connectivity though synapse formation maintenance. Here, we show controls vesicles organelles along axon mice cortical projection in vitro. Moreover, suppression ortholog, dacapo,...
Abstract Amyotrophic lateral sclerosis (ALS) is a devastating disease, characterized by extremely rapid loss of motor neurons. Our studies over the last decade have established CD4 + T cells as important players in central nervous system maintenance and repair. Those results, together with recent findings that play protective role mouse models ALS, led us to current hypothesis T‐cell malfunction may develop parallel neuron dysfunction. Here, we tested this assessing thymic function, which...
Silicon-based photodetectors cannot distinguish between different wavelengths. Therefore, these detectors relay on color-specific filters to achieve color separation. Color add complexity sensitive device fabrication, and hinder miniaturization of such devices. Here, we report an ultrasmall (as small as ∼20 nm by 300 nm), red-green-blue-violet (RGBV) filter-free spectrally gated field effect transistor (SGFET) detectors. These are based organic-silicon nanowire hybrid FET devices, capable...
Hypotrichosis simplex of the scalp (HSS) is characterized by progressive loss hair that results in almost complete baldness at a young age. HSS often caused dominant nonsense mutations CDSN encoding corneodesmosin, leading to formation an amyloid‐like material, which interferes with normal follicle cycle. As gentamicin has been shown mediate ribosomal read‐through, we aimed ascertain its therapeutic efficacy small series patients carrying recurrent mutation . We used green fluorescence...