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Articles 1 - 6 of 6
Full-Text Articles in Medicine and Health Sciences
Ampk Modulation Ameliorates Dominant Disease Phenotypes Of Ctrp5 Variant In Retinal Degeneration, Kiyoharu J. Miyagishima, Ruchi Sharma, Malika Nimmagadda, Katharina Clore-Gronenborn, Zoya Qureshy, Davide Ortolan, Devika Bose, Mitra Farnoodian, Congxiao Zhang, Andrew Fausey, Yuri V. Sergeev, Mones Abu-Asab, Bokkyoo Jun, Khanh V. Do, Marie Audrey Kautzman Guerin, Jorgelina Calandria, Aman George, Bin Guan, Qin Wan, Rachel C. Sharp
Ampk Modulation Ameliorates Dominant Disease Phenotypes Of Ctrp5 Variant In Retinal Degeneration, Kiyoharu J. Miyagishima, Ruchi Sharma, Malika Nimmagadda, Katharina Clore-Gronenborn, Zoya Qureshy, Davide Ortolan, Devika Bose, Mitra Farnoodian, Congxiao Zhang, Andrew Fausey, Yuri V. Sergeev, Mones Abu-Asab, Bokkyoo Jun, Khanh V. Do, Marie Audrey Kautzman Guerin, Jorgelina Calandria, Aman George, Bin Guan, Qin Wan, Rachel C. Sharp
School of Graduate Studies Faculty Publications
Late-onset retinal degeneration (L-ORD) is an autosomal dominant disorder caused by a missense substitution in CTRP5. Distinctive clinical features include sub-retinal pigment epithelium (RPE) deposits, choroidal neovascularization, and RPE atrophy. In induced pluripotent stem cells-derived RPE from L-ORD patients (L-ORD-iRPE), we show that the dominant pathogenic CTRP5 variant leads to reduced CTRP5 secretion. In silico modeling suggests lower binding of mutant CTRP5 to adiponectin receptor 1 (ADIPOR1). Downstream of ADIPOR1 sustained activation of AMPK renders it insensitive to changes in AMP/ATP ratio resulting in defective lipid metabolism, reduced Neuroprotectin D1(NPD1) secretion, lower mitochondrial respiration, and reduced ATP production. These metabolic …
Investigating The Role Of Adipor1 In Pro-Homeostatic Fatty Acid Metabolism Pathways, Eric Prestenburg, Alise Aucoin, Marie-Audrey Kautzmann-Guerin, Bokkyoo Jun, William Gordon, Nicolas Bazan
Investigating The Role Of Adipor1 In Pro-Homeostatic Fatty Acid Metabolism Pathways, Eric Prestenburg, Alise Aucoin, Marie-Audrey Kautzmann-Guerin, Bokkyoo Jun, William Gordon, Nicolas Bazan
Medical Student Research Poster Symposium
Docosahexaenoic acid (DHA, 22:6) is a substrate widely accepted as necessary for synthesizing very-long-chain polyunsaturated fatty acids (VLC-PUFAs), a class of lipids found in high concentrations in the retina. VLC-PUFAs are formed from 28:6 derived in the omega-3 fatty acid pathway involving eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid (DHA, 22:6) by a series of reactions catalyzed by the elongase ELOVL4 within the inner segments of the photoreceptor cells (PRCs). VLC-PUFAs are precursors to elovanoids (ELVs), which have been indicated to maintain homeostasis in the retina in response to inflammation and uncompensated oxidative stress (UOS). During these conditions, elovanoids are …
Investigating Neuroprotective Efficacy Of Lipid Mediators Neuroprotectin D1 (Npd1)And Resolvin D1 (Rvd1) On Behavioral Outcomes And Ischemic Penumbra, Kierany B. Shelvin, Madigan M. Reid, Larissa Khourtorova, Jeff Ji, William Lewis, Pranab Mukherjee, Ludmila Belayev, Nicolas G. Bazan
Investigating Neuroprotective Efficacy Of Lipid Mediators Neuroprotectin D1 (Npd1)And Resolvin D1 (Rvd1) On Behavioral Outcomes And Ischemic Penumbra, Kierany B. Shelvin, Madigan M. Reid, Larissa Khourtorova, Jeff Ji, William Lewis, Pranab Mukherjee, Ludmila Belayev, Nicolas G. Bazan
Medical Student Research Poster Symposium
Background: In the United States, stroke is the sixth leading cause of death, and a major cause of long-term disability. Ischemic stroke elicits a cascade of immune and neuroinflammatory responses that form an ischemic core and surrounding area (penumbra) which can be salvaged upon reperfusion within a limited period of time. Reperfusion signals the release of an essential omega-3 fatty acid, Docosahexaenoic acid (DHA) from injured neuronal cell membranes. DHA is converted into its derivatives, Neuroprotectin D1 (NPD1) via 15- lypoxygenase and Resolvin D1 (RvD1) via 15- and 5-lypoxygenase. These docosanoid lipid mediators have been shown to improve neurologic outcomes …
Enhancing Mask Activity In Dopaminergic Neurons Extends Lifespan In Flies, Xiaolin Tian
Enhancing Mask Activity In Dopaminergic Neurons Extends Lifespan In Flies, Xiaolin Tian
School of Medicine Faculty Publications
Dopaminergic neurons (DANs) are essential modulators for brain functions involving memory formation, reward processing, and decision-making. Here I demonstrate a novel and important function of the DANs in regulating aging and longevity. Overexpressing the putative scaffolding protein Mask in two small groups of DANs in flies can significantly extend the lifespan in flies and sustain adult locomotor and fecundity at old ages. This Mask-induced beneficial effect requires dopaminergic transmission but cannot be recapitulated by elevating dopamine production alone in the DANs. Independent activation of Gαs in the same two groups of DANs via the drug-inducible DREADD system also extends fly …
Elucidating The Structure And Functions Of Resolvin D6 Isomers On Nerve Regeneration With A Distinctive Trigeminal Transcriptome, Thang L. Pham, Azucena H. Kakazu, Jiucheng He, Robert Nshimiyimana, Nicos A. Petasis, Bokkyoo Jun, Nicolas G. Bazan, Haydee E.P. Bazan
Elucidating The Structure And Functions Of Resolvin D6 Isomers On Nerve Regeneration With A Distinctive Trigeminal Transcriptome, Thang L. Pham, Azucena H. Kakazu, Jiucheng He, Robert Nshimiyimana, Nicos A. Petasis, Bokkyoo Jun, Nicolas G. Bazan, Haydee E.P. Bazan
School of Medicine Faculty Publications
Innervation sustains cornea integrity. Pigment epithelium-derived factor (PEDF) plus docosahexaenoic acid (DHA) regenerated damaged nerves by stimulating the synthesis of a new stereoisomer of Resolvin D6 (RvD6si). Here, we resolved the structure of this lipid isolated from mouse tears after injured corneas were treated with PEDF + DHA. RvD6si synthesis was inhibited by fluvoxamine, a cytochrome P450 inhibitor, but not by 15- or 5-LOX inhibitors, suggesting that the 4- and 17-hydroxy of DHA have an RR- or SR-configuration. The two compounds were chemically synthesized. Using chiral phase HPLC, four peaks of RvD6si1-4 from tears were resolved. The RR-RvD6 standard eluted …
Glucocorticoid Receptor Antagonist Mifepristone Does Not Alter Innate Anxiety-Like Behavior In Genetically-Selected Marchigian Sardinian (Msp) Rats, Valentina Vozella, Bryan Cruz, Luis A. Natividad, Federica Benvenuti, Nazzareno Cannella, Scott Edwards, Eric P. Zorrilla, Roberto Ciccocioppo, Marisa Roberto
Glucocorticoid Receptor Antagonist Mifepristone Does Not Alter Innate Anxiety-Like Behavior In Genetically-Selected Marchigian Sardinian (Msp) Rats, Valentina Vozella, Bryan Cruz, Luis A. Natividad, Federica Benvenuti, Nazzareno Cannella, Scott Edwards, Eric P. Zorrilla, Roberto Ciccocioppo, Marisa Roberto
School of Graduate Studies Faculty Publications
Marchigian Sardinian alcohol-preferring (msP) rats serve as a unique model of heightened alcohol preference and anxiety disorders. Their innate enhanced stress and poor stress-coping strategies are driven by a genetic polymorphism of the corticotropin-releasing factor receptor 1 (CRF1) in brain areas involved in glucocorticoid signaling. The activation of glucocorticoid receptors (GRs) regulates the stress response, making GRs a candidate target to treat stress and anxiety. Here, we examined whether mifepristone, a GR antagonist known to reduce alcohol drinking in dependent rats, decreases innate symptoms of anxiety in msPs. Male and female msPs were compared to non-selected Wistar counterparts across three …