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Articles 541 - 570 of 746
Full-Text Articles in Pharmacy and Pharmaceutical Sciences
Genomics-Based Re-Examination Of The Taxonomy And Phylogeny Of Human And Simian Mastadenoviruses: An Evolving Whole Genomes Approach, Revealing Putative Zoonosis, Anthroponosis, And Amphizoonosis, June Kang, Ashrafali Mohamed Ismail, Shoaleh Dehghan, Jaya Rajaiya, Marc W. Allard, Haw Chuan Lim, David W. Dyer, James Chodosh, Donald Seto
Genomics-Based Re-Examination Of The Taxonomy And Phylogeny Of Human And Simian Mastadenoviruses: An Evolving Whole Genomes Approach, Revealing Putative Zoonosis, Anthroponosis, And Amphizoonosis, June Kang, Ashrafali Mohamed Ismail, Shoaleh Dehghan, Jaya Rajaiya, Marc W. Allard, Haw Chuan Lim, David W. Dyer, James Chodosh, Donald Seto
United States Food and Drug Administration: Publications
With the advent of high-resolution and cost-effective genomics and bioinformatics tools and methods contributing to a large database of both human (HAdV) and simian (SAdV) adenoviruses, a genomics-based re-evaluation of their taxonomy is warranted. Interest in these particular adenoviruses is growing in part due to the applications of both in gene transfer protocols, including gene therapy and vaccines, as well in oncolytic protocols. In particular, the re-evaluation of SAdVs as appropriate vectors in humans is important as zoonosis precludes the assumption that human immune system may be na€ıve to these vectors. Additionally, as impor- tant pathogens, adenoviruses are a model …
The Impact Of The Abuse-Deterrent Reformulation Of Extended-Release T Oxycontin On Prescription Pain Reliever Misuse And Heroin Initiation, Carolyn Wolff, William N. Dowd, Mir M. Ali, Chandler Mcclellan, Angelica Meinhofer, Lukas Glos, Ryan Mutter, Matthew Rosenberg, Andreas Schikc
The Impact Of The Abuse-Deterrent Reformulation Of Extended-Release T Oxycontin On Prescription Pain Reliever Misuse And Heroin Initiation, Carolyn Wolff, William N. Dowd, Mir M. Ali, Chandler Mcclellan, Angelica Meinhofer, Lukas Glos, Ryan Mutter, Matthew Rosenberg, Andreas Schikc
United States Food and Drug Administration: Publications
The introduction of abuse-deterrent OxyContin in 2010 was intended to reduce its misuse by making it more tamper resistant. However, some studies have suggested that this reformulation might have had unintended consequences, such as increases in heroin-related deaths. We used the 2005–2014 cross-sectional U.S. National Survey on Drug Use and Health to explore the impact of this reformulation on intermediate outcomes that precede heroin-related deaths for individuals with a history of OxyContin misuse. Our study sample consisted of adults who misused any prescription pain reliever prior to the reformulation of OxyContin (n = 81,400). Those who misused OxyContin prior to …
Development Of A Nicotinic Acetylcholine Receptor Nachr Α7 Binding Activity Prediction Model, Sugunadevi Sakkiah, Carmine Leggett, Bohu Pan, Wenjing Guo, Luis G. Valerio Jr., Huixiao Hong
Development Of A Nicotinic Acetylcholine Receptor Nachr Α7 Binding Activity Prediction Model, Sugunadevi Sakkiah, Carmine Leggett, Bohu Pan, Wenjing Guo, Luis G. Valerio Jr., Huixiao Hong
United States Food and Drug Administration: Publications
Despite the well-known adverse health effects associated with tobacco use, addiction to nicotine found in tobacco products causes difficulty in quitting among users. Nicotinic acetylcholine receptors (nAChRs) are the physiological targets of nicotine and facilitate addiction to tobacco products. The nAChR-α7 subtype plays an important role in addiction; therefore, predicting the binding activity of tobacco constituents to nAChR-α7 is an important component for assessing addictive potential of tobacco constituents. We developed an α7 binding activity prediction model based on a large training data set of 843 chemicals with human α7 binding activity data extracted from PubChem and ChEMBL. The model …
Nanoscale Interaction Of Recg With Mobile Fork Dna, Zhiqiang Sun, Yaqing Wang, Piero R. Bianco, Yuri L. Lyubchenko
Nanoscale Interaction Of Recg With Mobile Fork Dna, Zhiqiang Sun, Yaqing Wang, Piero R. Bianco, Yuri L. Lyubchenko
Journal Articles: Pharmaceutical Sciences
RecG DNA helicase is a guardian of the bacterial genome where it dominates stalled DNA replication fork rescue. The single-stranded DNA binding protein (SSB) is involved in this process and promotes the binding of RecG to stalled replication forks. Atomic force microscopy (AFM) was used to investigate the interaction of RecG and SSB on a mobile fork substrate capable of being regressed. In the absence of proteins, the fork undergoes spontaneous dynamics between two states, defined by the length of the DNA complementarity at the fork. The binding of SSB does not affect these dynamics as it binds to single-stranded …
Neuronal-Derived Extracellular Vesicles Are Enriched In The Brain And Serum Of Hiv-1 Transgenic Rats, Raghubendra S. Dagur, Ke Liao, Susmita Sil, Fang Niu, Zhiqiang Sun, Yuri L. Lyubchenko, Eric S. Peebles, Guoku Hu, Shilpa Buch
Neuronal-Derived Extracellular Vesicles Are Enriched In The Brain And Serum Of Hiv-1 Transgenic Rats, Raghubendra S. Dagur, Ke Liao, Susmita Sil, Fang Niu, Zhiqiang Sun, Yuri L. Lyubchenko, Eric S. Peebles, Guoku Hu, Shilpa Buch
Journal Articles: Pharmaceutical Sciences
Despite the efficacy of combination antiretroviral therapy (ART) in controlling human immunodeficiency virus (HIV-1) replication, cytotoxic viral proteins such as HIV-1 transactivator of transcription (Tat) persist in tissues such as the brain. Although HIV-1 does not infect neuronal cells, it is susceptible to viral Tat protein-mediated toxicity, leading to neuroinflammation that underlies HIV-associated neurocognitive disorders (HAND). Given the role of extracellular vesicles (EVs) in both cellular homoeostasis and under pathological conditions, we sought to investigate the alterations in the quantity of neuronal-derived EVs in the brain–as defined by the presence of cell adhesion molecule L1 (L1CAM) and to evaluate the …
The Current State Of Drug Repurposing And Rare Diseases: An Interview With Paul Trippier, Paul C. Trippier
The Current State Of Drug Repurposing And Rare Diseases: An Interview With Paul Trippier, Paul C. Trippier
Journal Articles: Pharmaceutical Sciences
Paul Tripper is an Associate Professor of Medicinal Chemistry at the University of Nebraska Medical Center (UNMC, NE, USA) and an Editorial Board member of Future Drug Discovery. Here, he speaks to Managing Editor Francesca Lake about drug repurposing, focusing on the key challenges, its application to rare diseases and what we can look forward to in the future.
Development Of Abuse Deterrent Formulations Using Hot Melt Extrusion, Pavan Kumar Nukala
Development Of Abuse Deterrent Formulations Using Hot Melt Extrusion, Pavan Kumar Nukala
Theses and Dissertations
In recent years prescription drug diversion, misuse, abuse represent a growing problem for the United States. Oral ingestion, snorting, injection are most commonly employed routes of abuse. To circumvent this problem hot melt extrusion (HME) was employed to prepare abuse deterrent formulation (ADF). Abuse Deterrent Immediate Release Egg-Shaped Tablet Using 3D Printing Technology: Quality by Design to Optimize Drug Release and Extraction. In current work, we developed egg-shaped tablet (egglet) using fused deposition modeling (FDM) 3D printing. Drug-loaded polymeric filaments (1.5 mm) were prepared using HME followed by printing into egglets of different sizes and infill densities. Based on printability, …
Severe Food Restriction Activates The Central Renin Angiotensin System, Aline Maria De Souza, Andrea Linares, Robert C. Speth, Glenda V. Campos, Hong Ji, Deoclécio Chianca, Kathryn Sandberg, Rodrigo C. De Menezes
Severe Food Restriction Activates The Central Renin Angiotensin System, Aline Maria De Souza, Andrea Linares, Robert C. Speth, Glenda V. Campos, Hong Ji, Deoclécio Chianca, Kathryn Sandberg, Rodrigo C. De Menezes
HPD Articles
We previously showed that 2 weeks of a severe food restricted (sFR) diet (40% of the caloric intake of the control (CT) diet) up-regulated the circulating renin angiotensin (Ang) system (RAS) in female Fischer rats, most likely as a result of the fall in plasma volume. In this study, we investigated the role of the central RAS in the mean arterial pressure (MAP) and heart rate (HR) dysregulation associated with sFR. Although sFR reduced basal mean MAP and HR, the magnitude of the pressor response to intracerebroventricular (icv) microinjection of Ang-[1-8] was not affected; however, HR was 57 ± 13 …
Characterization Of Antibiotic Use And Culture Data In Covid-19 Pandemic Patients, Ashley Logan Pharmd, Stacy Clore Pharmd, Bcps, Alissa Keillor Pharmd
Characterization Of Antibiotic Use And Culture Data In Covid-19 Pandemic Patients, Ashley Logan Pharmd, Stacy Clore Pharmd, Bcps, Alissa Keillor Pharmd
Parkview Pharmacy Department
Poster Presentation
2020 ASHP Midyear Clinical Meeting / Virtual / Poster # RP-609
Objective: The objective of this study was to identify the prevalence of bacterial, viral, or fungal coinfections and to describe the empiric antimicrobial regimens in patients with confirmed COVID-19.
Assessing Duration Of Therapy Recommendations Based On Clostridium Difficile Guidelines Within The Parkview Health System, Curtis Stump Pharmd, Trent Towne Pharmd, Bcps, Aubrey Mills Pharmd
Assessing Duration Of Therapy Recommendations Based On Clostridium Difficile Guidelines Within The Parkview Health System, Curtis Stump Pharmd, Trent Towne Pharmd, Bcps, Aubrey Mills Pharmd
Parkview Pharmacy Department
2020 ASHP Midyear Clinical Meeting / Virtual / Poster
Objective: The objective of this study was to evaluate the appropriateness of first episode CDI treatment (non-severe and severe cases) within the Parkview health system
Evaluation Of Pharmacy To Dose Heparin Protocol In Neurological Conditions, Leslie Siegel Pharmd, Timothy L. Johnston Pharmd, Karen Dunkelberger Bs Pharm, Mshi, Cpps
Evaluation Of Pharmacy To Dose Heparin Protocol In Neurological Conditions, Leslie Siegel Pharmd, Timothy L. Johnston Pharmd, Karen Dunkelberger Bs Pharm, Mshi, Cpps
Parkview Pharmacy Department
2020 ASHP Midyear Clinical Meeting / Virtual / Poster
The objective of this study was to assess the safety and efficacy of the current pharmacy to dose heparin protocol for neurological conditions.
Evaluation Of The Diagnosis And Treatment Of Asymptomatic Bacteriuria At A Community Hospital, Halie Mcmillan, Abby L. Todt Pharmd, Bcps, Sarah Ferrell Pharmd, Jamie Gaul Pharmd, Bcps
Evaluation Of The Diagnosis And Treatment Of Asymptomatic Bacteriuria At A Community Hospital, Halie Mcmillan, Abby L. Todt Pharmd, Bcps, Sarah Ferrell Pharmd, Jamie Gaul Pharmd, Bcps
Parkview Pharmacy Department
2020 ASHP Midyear Clinical Meeting / Virtual Meeting / Poster #SP-511
Objective: To evaluate the diagnosis and treatment of asymptomatic bacteriuria (ASB) within a community hospital setting.
Evaluation Of Dexmedetomidine Use As An Adjunctive Therapy In The Management Of Alcohol Withdrawal Syndrome, Zsanett Kormanyos Pharmd, Dustin D. Linn Pharmd, Bcps, Bcccp, Jillian Coons Pharmd, Bcps
Evaluation Of Dexmedetomidine Use As An Adjunctive Therapy In The Management Of Alcohol Withdrawal Syndrome, Zsanett Kormanyos Pharmd, Dustin D. Linn Pharmd, Bcps, Bcccp, Jillian Coons Pharmd, Bcps
Parkview Pharmacy Department
2020 ASHP Midyear Clinical Meeting / New Orleans, Louisiana / Poster # RP-606
The objective of this medication use evaluation (MUE) was to assess the utilization and outcomes associated with dexmedetomidine in the treatment of alcohol withdrawal syndrome
The Value Driven Pharmacist: Basics Of Access, Cost, And Quality 2nd Edition, Carriann Smith, Annette Mcfarland, Chad Knoderer, Joseph Jordan, Trish Devine, Jessica Wilhoite
The Value Driven Pharmacist: Basics Of Access, Cost, And Quality 2nd Edition, Carriann Smith, Annette Mcfarland, Chad Knoderer, Joseph Jordan, Trish Devine, Jessica Wilhoite
Butler University Books
No abstract provided.
2020 Edition, Southwestern Oklahoma State University
2020 Edition, Southwestern Oklahoma State University
The Sig
The Sig Newsletter from the Southwestern Oklahoma State University College of Pharmacy - 2020 Edition
Long-Term Negative Emotional Outcomes Of Warzone Tbi, Jennifer J. Vasterling, Mihaela Aslan, Susan P. Proctor, John Ko, Xenia Leviyah, John Concato
Long-Term Negative Emotional Outcomes Of Warzone Tbi, Jennifer J. Vasterling, Mihaela Aslan, Susan P. Proctor, John Ko, Xenia Leviyah, John Concato
United States Food and Drug Administration: Publications
Objective: Many veterans of the Iraq and Afghanistan Wars have experienced traumatic brain injury (TBI). Although prior work has examined associations between TBI and development of psychi- atric syndromes, less is known about associations between TBI and component emotions constituting these syndromes, especially in the long term. The purpose of this study was to examine the long-term emotional consequences of deployment-related TBI.
Methods: As part of VA Cooperative Studies Program #566, we assessed a sample of n1⁄4456US Army soldiers prior to an index deployment to Iraq, and again an average of 8.3 years (SD1⁄42.4years) after their deployment for a long-term …
Jackrabbits Script & Scope, Winter 2020, College Of Pharmacy And Allied Health Professions
Jackrabbits Script & Scope, Winter 2020, College Of Pharmacy And Allied Health Professions
Jackrabbits Script and Scope (Formerly called College of Pharmacy and Allied Health Professions Magazine)
[Page] 4 Haarberg Chair in Cancer Research
[Page] 7 Opioid Addiction Treatment
[Page] 8 Medication Adherence
[Page] 9 Nyberg Breaks Ground
[Page] 10 New Tumor Model Developed
[Page] 12 Scholarships
[Page] 14 Medical Laboratory Science White Coat
[Page] 16 Distinguished Alum Berry Markl
[Page] 17 Remembering Stanley Shaw
[Page] 18 Presenting at Congressional Briefing
[Page] 20 New Faculty/Staff
[Page] 23 Quiz Bowl Standouts
[Page] 24 Student Tabbed for Elite Program
[Page] 25 Kuddos to Gamma Kappa Chapter
[Page] 26 Rising High in Kappa Psi
[Page] 27 Fall Convocation & Research Day
[Page] 28 Academic Assessment
[Page] 29 Department of Allied …
Chemical Space Exploration Around Thieno[3,2-D]Pyrimidin-4(3h)-One Scaffold Led To A Novel Class Of Highly Active Clostridium Difficile Inhibitors, Xuwei Shao
Theses and Dissertations
Clostridium difficile infection (CDI) is the leading cause of healthcare-associated infection in the United States. Therefore, development of novel treatments for CDI is a high priority. Toward this goal, we began in vitro screening of a structurally diverse in-house library of 67 compounds against two pathogenic C. difficile strains (ATCC BAA 1870 and ATCC 43255), which yielded a hit compound, 2-methyl-8-nitroquinazolin-4(3H)-one (2) with moderate potency (MIC = 312/156 µM). Optimization of 2 gave lead compound 6a (2-methyl-7-nitrothieno[3,2-d]pyrimidin-4(3H)-one) with improved potency (MIC = 19/38 µM), selectivity over normal gut microflora, CC50s >606 µM against mammalian cell lines, and acceptable stability in …
Nvestigation Of Dissolution And Dispersion Behavior Of Ritonavir From Amorphous Solid Dispersion, Nitprapa Siriwannakij
Nvestigation Of Dissolution And Dispersion Behavior Of Ritonavir From Amorphous Solid Dispersion, Nitprapa Siriwannakij
Theses and Dissertations
The aim of this study was to develop ritonavir amorphous solid dispersion (ASD) formulation, investigate its aqueous dissolution and dispersion behavior, and predict potential pharmacokinetic parameters by in-silico modeling. The binary/ternary ASDs of ritonavir with PVPVA or HPMCAS-MG in the absence or presence of surfactants were prepared by using the hot-melt extrusion method. The amount of ritonavir was fixed at 20 %w/w, while amount of polymer and surfactant in the formulation was varied. The film-casting technique was used to confirm the miscibility of drug and polymer in the absence and presence of surfactant in different formulations. PXRD and DSC analyze …
Continuous Salt Synthesis And Granulation Using Single Step Twin Screw Extrusion Process, Jaydip Vasoya
Continuous Salt Synthesis And Granulation Using Single Step Twin Screw Extrusion Process, Jaydip Vasoya
Theses and Dissertations
In the present investigation, a continuous, and novel organic solvent-free approach for the synthesis of pharmaceutical salts using the twin screw extruder (TSE) is reported. Although the method offers distinct advantages such as solvent free synthesis and short processing time over the conventional salt synthesis, the produced salts usually require further processing into granules before they can be compressed into tablets or filled into capsules, which makes the final product manufacturing non-continuous. This report, for the first time, describes a process of combining salt synthesis and granulation into a single-step using a TSE. Cinnarizine, a model poorly water-soluble weakly basic …
Oil/Water Nanoemulsion Biodistribution In Mice Upon Intravenous Administration, Jiayi Chen
Oil/Water Nanoemulsion Biodistribution In Mice Upon Intravenous Administration, Jiayi Chen
Theses and Dissertations
The present study aimed to explore the biodistribution of O/W nanoemulsions (NE) upon intravenous administration. Three NEs were prepared with distinctive droplet sizes: SE (29 ± 1 nm), ME (214 ± 2 nm) and LE (883 ± 16 nm) without overlapping of the size distribution. Kolliphor® HS15 was used as the only surfactant for these three NEs, so that their droplets had similar surface structure. The NEs droplet size was stable under room temperature for minimum 3 days in phosphate buffer saline (PBS) and in mice plasma in vitro for 4-hour at 37°C. A lipophilic fluorescent dye, 1, 1’-dioctadecyl-3, 3, …
Development, Evaluation And Application Of Insulin Solution And Film Dosage Forms For Sublingual Administration, Anuja Paprikar
Development, Evaluation And Application Of Insulin Solution And Film Dosage Forms For Sublingual Administration, Anuja Paprikar
Theses and Dissertations
The major barrier for sublingual absorption of large molecules like insulin is low permeability owing to the hydrophilic nature of insulin. One approach to overcome this barrier is to sublingually co-administer insulin with permeation enhancers (HPβCD and poloxamer 188). In vitro performance of permeation enhancers was screened across cellulose acetate membrane to select the concentrations of both enhancers, which were further evaluated across four models (MatTek tissue model, MDCK cell line, rat and porcine esophagus). The insulin solution with combination of HPβCD (5%) and poloxamer 188 (0.5%) indicates higher permeation as compared to that of only insulin across all the …
Chemical Synthesis And Evaluation Of Azotochelin Analogs As Anticancer Agents And Their Ability To Reverse Anticancer Drug Resistance, Nishant Karadkhelkar
Chemical Synthesis And Evaluation Of Azotochelin Analogs As Anticancer Agents And Their Ability To Reverse Anticancer Drug Resistance, Nishant Karadkhelkar
Theses and Dissertations
Cancer has been plaguing the humanity for several decades. In the meanwhile, multi-drug resistance (MDR) is causing abatement of effective therapeutic drugs, necessitating discovery of new class of anticancer agents. Natural products have been proved to be a promising source of structurally new anticancer agents. A specific class of bacterial secondary metabolites, named siderophores have been explored as potential anticancer agents. Enterobactin is one of the most studied siderophores as a potential anticancer agent. Azotochelin is a structurally similar but structurally simpler siderophore compared to enterobactin. Our research project focused on the evaluation of the structure activity relationship assessment of …
Understanding The Healthcare Experiences And Needs Of African Immigrants In The United States: A Scoping Review, Ogbonnaya I. Omenk, Dennis P. Watson, Hugh C. Hendrie
Understanding The Healthcare Experiences And Needs Of African Immigrants In The United States: A Scoping Review, Ogbonnaya I. Omenk, Dennis P. Watson, Hugh C. Hendrie
Scholarship and Professional Work – COPHS
Background: Africans immigrants in the United States are the least-studied immigrant group, despite the research and policy efforts to address health disparities within immigrant communities. Although their healthcare experiences and needs are unique, they are often included in the “black” category, along with other phenotypically-similar groups. This process makes utilizing research data to make critical healthcare decisions specifically targeting African immigrants, difficult. The purpose of this Scoping Review was to examine extant information about African immigrant health in the U.S., in order to develop lines of inquiry using the identified knowledge-gaps.
Methods: Literature published in the English language between 1980 …
College Of Pharmacy 2020, Nova Southeastern University
College Of Pharmacy 2020, Nova Southeastern University
Health Professions Divisions Course Catalogs and Course Descriptions
No abstract provided.
Bill Gatton College Of Pharmacy Viewbook - 2020, Bill Gatton College Of Pharmacy, East Tennessee State University
Bill Gatton College Of Pharmacy Viewbook - 2020, Bill Gatton College Of Pharmacy, East Tennessee State University
Bill Gatton College of Pharmacy Miscellaneous Publications
No abstract provided.
Postnatal Catch-Up Growth Leads To Higher P66shc And Mitochondrial Dysfunction., Shelby Oke, Gurjeev Sohi, Daniel Barry Hardy
Postnatal Catch-Up Growth Leads To Higher P66shc And Mitochondrial Dysfunction., Shelby Oke, Gurjeev Sohi, Daniel Barry Hardy
Physiology and Pharmacology Publications
Epidemiological data suggest an inverse relationship between birth weight and long-term metabolic deficits, which is exacerbated by postnatal catch-up growth. We have previously demonstrated that rat offspring subject to maternal protein restriction (MPR) followed by catch-up growth exhibit impaired hepatic function and ER stress. Given that mitochondrial dysfunction is associated with various metabolic pathologies, we hypothesized that altered expression of p66Shc, a gatekeeper of oxidative stress and mitochondrial function, contributes to the hepatic defects observed in MPR offspring. To test this hypothesis, pregnant Wistar rats were fed a control (20% protein) diet or an isocaloric low protein (8%; LP) diet …
Quantification Of Joint Blood Flow By Dynamic Contrast-Enhanced Near-Infrared Spectroscopy: Application To Monitoring Disease Activity In A Rat Model Of Rheumatoid Arthritis, Seva Ioussoufovitch, Laura B. Morrison, Lise Desjardins, Jennifer A. Hadway, Keith St Lawrence, Ting Yim Lee, Frank Beier, Mamadou Diop
Quantification Of Joint Blood Flow By Dynamic Contrast-Enhanced Near-Infrared Spectroscopy: Application To Monitoring Disease Activity In A Rat Model Of Rheumatoid Arthritis, Seva Ioussoufovitch, Laura B. Morrison, Lise Desjardins, Jennifer A. Hadway, Keith St Lawrence, Ting Yim Lee, Frank Beier, Mamadou Diop
Physiology and Pharmacology Publications
No abstract provided.
Nanopore-Based Metagenomic Comparison Of Airway Colonizers Between Cystic Fibrosis Patients And Healthy Individuals, Anita Samadabadi
Nanopore-Based Metagenomic Comparison Of Airway Colonizers Between Cystic Fibrosis Patients And Healthy Individuals, Anita Samadabadi
Honors Undergraduate Theses
Cystic fibrosis (CF) is an autosomal recessive genetic disorder involving a mutation in the CF transmembrane conductance regulator protein (CFTR), which causes dysfunctional transport of chloride ions across cell membranes. CF affects multiple body systems and a few of its symptoms include chronic cough, difficulty breathing, obstructive airway disease, bacterial pulmonary infections, maldigestion, malabsorption, pancreatitis, and male infertility. Until recently, treatment options have been limited to alleviating symptoms, but a new classification of drugs, CFTR modulators, provide an opportunity to slow the progression of the disease and improve clinical outcomes. The effect of CFTR modulators may be attributed to the …
Interaction Of Aβ42 With Membranes Triggers The Self-Assembly Into Oligomers, Siddhartha Banerjee, Mohtadin Hashemi, Karen Zagorski, Yuri L. Lyubchenko
Interaction Of Aβ42 With Membranes Triggers The Self-Assembly Into Oligomers, Siddhartha Banerjee, Mohtadin Hashemi, Karen Zagorski, Yuri L. Lyubchenko
Journal Articles: Pharmaceutical Sciences
The self-assembly of amyloid β (Aβ) proteins into oligomers is the major pathogenic event leading to Alzheimer's disease (AD). Typical in vitro experiments require high protein concentrations, whereas the physiological concentration of Aβ is in the picomolar to low nanomolar range. This complicates the translation of results obtained in vitro to understanding the aggregation process in vivo. Here, we demonstrate that Aβ42 self-assembles into aggregates on membrane bilayers at low nanomolar concentrations - a pathway in which the membrane plays the role of a catalyst. Additionally, physiological ionic conditions (150 mM NaCl) significantly enhance on-membrane aggregation, leading to the rapid …