A5050292747- Computational Drug Discovery Methods
- Cholinesterase and Neurodegenerative Diseases
- Alzheimer's disease research and treatments
- Marine Sponges and Natural Products
- Seaweed-derived Bioactive Compounds
- Innovative Microfluidic and Catalytic Techniques Innovation
- Chemical Synthesis and Analysis
- SARS-CoV-2 and COVID-19 Research
- Complement system in diseases
- Steroid Chemistry and Biochemistry
- Photoreceptor and optogenetics research
- Memory and Neural Mechanisms
- interferon and immune responses
- Neuroscience and Neuropharmacology Research
- Silicone and Siloxane Chemistry
- Cellular transport and secretion
- Coral and Marine Ecosystems Studies
- Estrogen and related hormone effects
- Sirtuins and Resveratrol in Medicine
- Organic Chemistry Cycloaddition Reactions
- Nanofabrication and Lithography Techniques
- 14-3-3 protein interactions
- Catalytic Cross-Coupling Reactions
- Protein Kinase Regulation and GTPase Signaling
- Sphingolipid Metabolism and Signaling
University of California, Los Angeles
2015-2024
Foundation for Psychocultural Research
2015-2024
Alzheimer’s Disease Neuroimaging Initiative
2023
Buck Institute for Research on Aging
2013
Dominican University of California
2013
Stanford University
1985
Abstract We describe here the results from testing of a small molecule first-in-class apolipoprotein E4 (ApoE4)-targeted sirtuin1 (SirT1) enhancer, A03, that increases levels neuroprotective enzyme SirT1 while not affecting neurotoxic sirtuin 2 (SirT2) in vitro ApoE4-transfected cells. A03 was identified by high-throughput screening (HTS) and found to be orally bioavailable brain penetrant. In vivo , treatment increased hippocampus 5XFAD-ApoE4 (E4FAD) Alzheimer’s disease (AD) model mice...
We report the discovery of a novel class compounds that function as dual inhibitors enzymes neutral sphingomyelinase-2 (nSMase2) and acetylcholinesterase (AChE). Inhibition these provides unique strategy to suppress propagation tau pathology in treatment Alzheimer's disease (AD). describe key SAR elements affect relative nSMase2 and/or AChE inhibitor effects potency, addition identification two analogs release tau-bearing exosomes vitro vivo. Identification nSMase2/AChE represents new...
A systematic approach was used to identify AβPP-selective BACE inhibitors (ASBI) and evaluate their in vivo ability modulate AβPP processing selectively. We identified a bioflavonoid nutritional supplement as molecular lead that acts an ASBI cell models, show increasing brain levels of this through pro-drug leads reduction Aβ42 Alzheimer's disease mouse model. ASBIs represent novel class candidate therapeutic agents for disease.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSterols in marine invertebrates. 49. Isolation and structure elucidation of eight new polyhydroxylated sterols from the soft coral Sinularia dissectaBarbara M. Jagodzinska, James S. Trimmer, William Fenical, Carl DjerassiCite this: J. Org. Chem. 1985, 50, 9, 1435–1439Publication Date (Print):May 1, 1985Publication History Published online1 May 2002Published inissue 1...
Brain rhythms provide the timing for recruitment of brain activity required linking together neuronal ensembles engaged in specific tasks. The γ-oscillations (30 to 120 Hz) orchestrate circuits underlying cognitive processes and working memory. These oscillations are reduced numerous neurological psychiatric disorders, including early decline Alzheimer's disease (AD). Here, we report on a potent brain-permeable small molecule, DDL-920 that increases improves cognition/memory mouse model AD,...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSterols in marine invertebrates. 51. Isolation and structure elucidation of C-18 functionalized sterols from the soft coral Sinularia dissectaBarbara M. Jagodzinska, James S. Trimmer, William Fenical, Carl DjerassiCite this: J. Org. Chem. 1985, 50, 16, 2988–2992Publication Date (Print):August 1, 1985Publication History Published online1 May 2002Published inissue 1 August...
ABSTRACT Inhibition of amyloid precursor protein (APP) beta-site cleaving enzyme 1 (BACE1; BACE) has been a target for Alzheimer’s disease (AD) therapeutic development, but impaired by off-target effects clinically evaluated inhibitors, including inhibition cleavage non-APP substrates. Here, we report our identification BACE inhibitors series that are not only selective the APP substrate, also BACE1 as targeted enzyme. These APP-selective fluoro aminohydantoin (FAH) inhibitor compounds were...
Summary Brain rhythms provide the timing and concurrence of brain activity required for linking together neuronal ensembles engaged in specific tasks. In particular, γ-oscillations (30-120 Hz) orchestrate circuits underlying cognitive processes working memory. These oscillations are reduced numerous neurological psychiatric disorders, including early decline Alzheimer’s disease (AD). Here we report on a potent permeable small molecule, DDL-920 that increases improves cognition/memory mouse...
Alzheimer's Disease (AD) is characterized by neuronal and synaptic loss. One process that could contribute to this loss the intracellular caspase cleavage of amyloid precursor protein (APP) resulting in release toxic C-terminal 31-amino acid peptide APP-C31 along with production APPC31, full-length APP minus 31 amino acids. We previously found a mutation prevents ameliorated cognitive impairment murine AD model. Thus, inhibition reasonable target for new therapeutic development. In order...
Abstract Background Brain rhythms provide the timing for recruitment of brain activity required linking together neuronal ensembles engaged in specific tasks. The γ‐oscillations (30‐120 Hz) orchestrate circuits underlying cognitive processes and working memory. High temporal resolution recording methods, such as magnetoencephalography, have made it clear that Alzheimer’s disease (AD) patients, starting early mild impairment (MCI) stage, diminished even before Aβ load takes full effect....
This study describes the development of a new and rapid synthesis procedure for performing aryl benzyl substituted 2-methylquinazolin-4(3H)-one ring cyclization reaction. We utilized continuous-flow microfluidic reactor production quinazolinone derivatives humanin peptide mimetic screening hit in facile manner, offering cleaner reaction profile, high yield, quick scalability. Our results show power flow chemistry to this can be general utility synthesizing quinazolinone-containing...
SARS-CoV-2 requires two cysteine proteases for viral polypeptide processing to allow maturation and replication: the 3C-like protease also known as Main (Mpro) papain-like (PLpro). In addition its critical role in replication, PLpro removes post-translational modifications like ubiquitin interferon-stimulated gene product 15 (ISG15) from host proteins through deubiquitinase domain, leading immunosuppression increased ability of virus evade antiviral immune response. Through screening a...
Caspase cleavage of amyloid precursor protein (APP) and production APPneo C31 contributes to the pathology AD. Compounds that reduce therefore may be therapeutic benefit in Identification mechanisms by which any APPneo-lowering compounds exert their effects is also interest. In our initial studies (Zhang 2014) we identified a TrkA kinase inhibitor as lowering showed inhibition increases sAPP vivo. We are currently screening large UCLA compound library find brain-permeable potent inhibitors....
Decreases in the level of major longevity determinant sirtuin 1 (SirT1) have been associated with Alzheimer's Disease (AD) and expression a genetic risk factor for sporadic AD, apolipoprotein E4 (ApoE4) [Kumar et al. 2013 PLoS One 8(4):e61560; Theendakara PNAS 110(45):18303]. We previously identified compound - A03 that normalized SirT1 levels presence ApoE4 vitro. Here, we determined A03's efficacy enhancing brain improving memory vivo murine model AD wherein human targeted-replacement...
Tau, amyloid beta (Aβ), and alpha-synuclein (αSyn) pathology can be spread from cell-to-cell by oligomers also called seeds in Alzheimer's disease (AD) Parkinson's (PD). Exosomes, small extracellular vesicles (EVs) originated multivesicular bodies, are one of the mechanisms seed transfer, but they may play an important role clearance intercellular signaling. Functional biochemical composition exosomes depend on type metabolic state their cell origin biogenesis pathway. If proteopathic...
ABSTRACT SARS-CoV-2 requires two cysteine proteases for viral polypeptide processing to allow maturation and replication: the 3C-like protease also known as Main (M pro ) papain-like (PL ). In addition its critical role in replication, PL removes post-translational modifications like ubiquitin interferon-stimulated gene product 15 (ISG15) from host proteins through deubiquitinase domain, leading immunosuppression increased ability of virus evade antiviral immune response. Through screening a...
Abstract Durch Oxidation des Testosterons (I) wird die seco‐Ketosäure (II) dargestellt.