A5041008015- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Cholinesterase and Neurodegenerative Diseases
- Cholesterol and Lipid Metabolism
- Nuclear Receptors and Signaling
- Ion channel regulation and function
- Photoreceptor and optogenetics research
- Nicotinic Acetylcholine Receptors Study
- Lipid Membrane Structure and Behavior
- Receptor Mechanisms and Signaling
- Drug Transport and Resistance Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Computational Drug Discovery Methods
- Mitochondrial Function and Pathology
- Cellular transport and secretion
- Memory and Neural Mechanisms
- Metabolomics and Mass Spectrometry Studies
- Amyloidosis: Diagnosis, Treatment, Outcomes
- S100 Proteins and Annexins
- Peroxisome Proliferator-Activated Receptors
- Retinal Development and Disorders
- Glaucoma and retinal disorders
- Dementia and Cognitive Impairment Research
- Prion Diseases and Protein Misfolding
- Skin and Cellular Biology Research
Tel Aviv University
2014-2025
St Michaels Hospital
2017-2018
City of Hope
2004
Beckman Research Institute
2004
Sheba Medical Center
2001
Hebrew University of Jerusalem
1978
California Institute of Technology
1974-1976
Lawrence Berkeley National Laboratory
1973-1974
University of California, Berkeley
1973-1974
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMagnetic resonance studies of membrane and model systems. VI. Transbilayer asymmetry surface homogeneity mixed phospholipids in cosonicated vesiclesDaniel M. Michaelson, Alan F. Horwitz, Melvin P. KleinCite this: Biochemistry 1973, 12, 14, 2637–2645Publication Date (Print):July 3, 1973Publication History Published online1 May 2002Published inissue 3 July...
The APOE ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). ApoE protein aggregation plays a central role in AD pathology, including accumulation of β-amyloid (Aβ). Lipid-poor ApoE4 prone to aggregate and lipidating protects it from aggregation. mechanisms regulating vivo are surprisingly not known. lipidation controlled by activity ATP binding cassette A1 (ABCA1). ABCA1 recycling degradation regulated ADP-ribosylation 6 (ARF6). We found that promoted...
Apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for Alzheimer's disease (AD), is less lipidated than its corresponding AD-benign form, apoE3, and it has been suggested that pathological effects of apoE4 are mediated by lipid-related mechanisms. ATP-binding cassette transporters A1 G1 (ABCA1 ABCG1, respectively) important apoE-lipidating proteins. The expression these proteins, as well apoE, controlled transcription regulation retinoid X receptor (RXR)–liver (LXR) system. In...
The allele ɛ4 of apolipoprotein E (apoE4) is the most prevalent genetic risk factor for Alzheimer's disease (AD) and therefore a promising therapeutic target. Human animal model studies suggest that apoE4 hypolipidated; accordingly, we have previously shown retinoid X receptor (RXR) agonist bexarotene upregulates ABCA1, main apoE-lipidating protein, resulting in increased lipidation apoE4, subsequent reversal pathological effects namely: accumulation Aβ42 hyperphosphorylated tau, as well...
APOE4 is a major risk factor for sporadic Alzheimer's disease; however, it unclear how exerts its pathological effects. Others and we have previously shown that autophagy impaired in compared to APOE3 astrocytes, demonstrated differences the expression of mitochondrial dynamics proteins brains transgenic mice. Here, investigated effect on several aspects function network dynamics, including fusion, fission, mitophagy, specifically astrocytes. We found astrocytes differ their suggesting...
Alzheimer's disease (AD) is characterized by toxic protein accumulation in the brain. Ubiquitination essential for clearance cells, making altered ubiquitin signaling crucial AD development. A defective variant, B + 1 (UBB+1), created a non-hereditary RNA frameshift mutation, found all patient brains post-mortem. We now detect UBB+1 human during early stages. Our study employs 3D neural culture platform derived from progenitors, demonstrating that alone induces extracellular amyloid-β (Aβ)...
<b><i>Background and Objective:</i></b> The authors recently reported that the <i>APOE</i> ε4 allele is associated with significantly greater progression of disability in a 2-year follow-up patients MS. In this study, these findings are substantiated extended much larger group followed for up to 40 years. <b><i>Methods:</i></b> Two hundred five clinically definite MS who were genotyped carrier state included. Groups (n = 41) without 164) alleles compared latency expanded status scale (EDSS)...
Abstract: Phosphatidylinositol‐specific phospholipase C (PIPLC) quantitatively solubilizes acetylcholinesterase (AChE) from purified synaptic plasma membranes and intact synaptosomes of Torpedo ocellata electric organ. The solubilized AChE migrates as a single peak sedimentation coefficient 7.OS upon sucrose gradient centrifugation, corresponding to subunit dimer. catalytic polypeptide is the only detectably soubilized by PIPLC. This selective removal does not affect amount acetylcholine...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHead group modulation of membrane fluidity in sonicated phospholipid dispersionsD. M. Michaelson, A. F. Horwitz, and P. KleinCite this: Biochemistry 1974, 13, 12, 2605–2612Publication Date (Print):June 1, 1974Publication History Published online1 May 2002Published inissue 1 June 1974https://pubs.acs.org/doi/10.1021/bi00709a021https://doi.org/10.1021/bi00709a021research-articleACS PublicationsRequest reuse permissionsArticle...
The allele E4 of apolipoprotein E (apoE4), the most prevalent genetic risk factor for Alzheimer's disease, is associated histopathologically with elevated levels brain amyloid. This led to suggestion that pathological effects apoE4 are mediated by cross-talk interactions amyloid β peptide (Aβ), which accentuate cascade. mechanisms underlying Aβ-mediated unknown. We have shown recently inhibition Aβ-degrading enzyme neprilysin in brains wild-type apoE3 and mice results rapid similar...
Abstract Background Recent findings suggest that the pathological effects of apoE4, most prevalent genetic risk factor for Alzheimer’s disease (AD), start many years before onset and are already detectable at a young age. In present study we investigated extent to which such cognitive impairments also occur in apoE4 mice. Results This revealed levels presynaptic glutamatergic vesicular transporter, VGlut, CA3, CA1, DG hippocampal subfields were lower neurons (4-month-old) apoE4-targeted...
The amyloid-β (Aβ) peptide, a major pathological hallmark of Alzheimer's disease (AD), undergoes cascade interactions resulting in the formation soluble aggregates and their conversion brain to insoluble deposits mature senile plaques. Furthermore, apoE4 isoform apolipoprotein E (apoE), which is genetic risk factor AD, associated with increased Aβ deposition. It not known how different amyloid are formed, contribute pathogenesis or affected by apoE4. To investigate initial aggregation stages...
Abstract Neurodegeneration in Alzheimer's disease (AD) is associated with the activation of neurogenesis. The mechanisms underlying this crosstalk between neuronal death and birth extent to which it affected by genetic risk factors AD are not known. We employed transgenic mice expressing human apolipoprotein E4 (apoE4), most prevalent factor for AD, or apoE3 (an AD‐benign allele), order examine hypothesis that apoE4 tilts balance neurogenesis cell favor latter. results showed an...
Association of purified acetylcholine receptor from Torpedo californica electroplax with lipids the same organism results in a vesicular membrane system which protein is oriented so that all neurotoxin binding sites appear to be on outer surface. The reconstituted chemically excitable by and carbamylcholine, as measured 22 Na + efflux. This excitability specifically blocked antagonist α-bungarotoxin. These demonstrate macromolecule contains not only specific neurotransmitter site but also...
Activation of the Ca2+/Mg2+ ATPase associated with highly purified Torpedo synaptic vesicles results in 45Ca2+ uptake. The accumulated is released by hypoosmotic buffer and Ca2+ ionophore A23187. Density-gradient centrifugation permeation chromatography reveal that vesicular acetylcholine membrane-bound co-migrate, thus implying transported into cholinergic vesicles. ATP-dependent uptake follows saturation kinetics, KmCa2+ = 50 microM, Vmax 3 +/- 0.3 nmol Ca2+/mg protein/min. Treatment...
Apolipoprotein E4 (apoE4) is the most prevalent genetic risk factor for Alzheimer's disease (AD). Epidemiological studies revealed that consumption of docosahexaenoic acid (DHA: 22 : 6 (ω3)), a major brain polyunsaturated fatty acid, protective fo
This study examined the effects of apolipoprotein E4 (APOE4), most prevalent genetic risk factor for Alzheimer's disease (AD), on proteins involved in mitochondrial dynamics and autophagy, hippocampus targeted replacement mice. Immunohistochemical measurements revealed that levels fusion-mediating protein, MFN1, were higher, whereas those corresponding fission-regulating DRP-1, lower ApoE4 mice than ApoE3 mice, indicating APOE4 is associated with increased fusion decreased fission. A similar...