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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Exploring The Roles Of Stress, Codon Usage, And Rna Modifications In Myotonic Dystrophy Type 1, Afrooz Golestanian Jan 2022

Exploring The Roles Of Stress, Codon Usage, And Rna Modifications In Myotonic Dystrophy Type 1, Afrooz Golestanian

Legacy Theses & Dissertations (2009 - 2024)

Myotonic dystrophy (DM), the most common form of muscular dystrophy, is a neuromuscular disease caused by microsatellite repeat expansions. It can represent a multi-systemic autosomal dominant disease with DM1 and DM2 subtypes. A cytosine-thymine-guanine (CTG) triplet repeat in the 3’ untranslated region (3’UTR) of myotonic dystrophy protein kinase (DMPK) gene causes DM1 disease, which leads to the production of a longer, abnormal and toxic mRNA. The toxic DMPK mRNA sequester the splicing proteins such as Muscle blind-like (MBNL) and rbFOX which leads to gene expression alteration. Repeat associated non-AUG (RAN) translation also occurs in DM1. Mitochondrial dysregulation has also been …


Ampa And Kainate Receptor-Potentiating Rna Aptamers, Janet L. Lynch May 2021

Ampa And Kainate Receptor-Potentiating Rna Aptamers, Janet L. Lynch

Legacy Theses & Dissertations (2009 - 2024)

Glutamate receptors act to bring about excitatory transmission in the central nervous system. The receptors are divided into two groups: ionotropic and metabotropic glutamate receptors. Ionotropic glutamate receptors are ion channels which are activated by an agonist such as glutamate or kainate. The main receptors in the ionotropic glutamate receptor family are the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate and N-methyl-D-aspartate (NMDA) receptors. In the central nervous system ionotropic glutamate receptors are found both pre- and postsynaptically. It has been found that most AMPA and NMDA receptors are postsynaptic receptors while the kainate receptors can be pre- or postsynaptic. Underactivity of these …


Heteromeric Assemblies Of Glua3 Flip And Flop Shows Differences In Their Channel Opening Kinetics, Nicholas Karl Jan 2018

Heteromeric Assemblies Of Glua3 Flip And Flop Shows Differences In Their Channel Opening Kinetics, Nicholas Karl

Legacy Theses & Dissertations (2009 - 2024)

Prior studies of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, including that of GluA3 AMPA receptor subunit, have shown that alternative mRNA splicing, which generates flip and flop variants with different amino acid sequences, gives rise to functional differences between the two variants. The goal of this MS thesis is to investigate the basic gating properties of the heteromeric complex channels formed from GluA2R/GluA3 AMPA receptor subunits and the different variants between the two subunits. The hypothesis to be tested is whether different GluA3 variants affect the channel gating properties when each of the variants is in a complex with the Q/R-site edited …


A Laser-Pulse Photolysis Study Of The Mechanism Of Potentiation Of The Glua2qflip Ampa Receptors By Cx546, Yu-Chuan Shen Jan 2017

A Laser-Pulse Photolysis Study Of The Mechanism Of Potentiation Of The Glua2qflip Ampa Receptors By Cx546, Yu-Chuan Shen

Legacy Theses & Dissertations (2009 - 2024)

Insufficient activity of the α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate ion channels is involved in neurological disorders and developmental problems, such as schizophrenia, one of the most serious psychiatric diseases. Use of regulatory agents to enhance AMPA receptor activity under the circumstance has been shown therapeutically beneficial. Specifically, small-molecule compounds generally termed as potentiators or positive modulators of AMPA receptors have long been pursued as drug candidates for a potential treatment of these neurological disorders and diseases. The goal of my MS thesis work is to investigate the mechanism of potentiation on AMPA receptor by a classic potentiator known as CX546. The …


Retinal Disease Modeling And Drug Screening Using Stem Cell Derived Retinal Pigment Epithelium, Janmeet Singh Saini Jan 2017

Retinal Disease Modeling And Drug Screening Using Stem Cell Derived Retinal Pigment Epithelium, Janmeet Singh Saini

Legacy Theses & Dissertations (2009 - 2024)

The eye is an intricate organ, possessing sensory receptors in the retina that are involved in visual perception. The retina consists primarily of the neural layer, referred to as the neural retina, and the pigmented layer, referred to as the retinal pigment epithelium (RPE). The neural retina and RPE develop and mature in a coordinated manner, and depend on each other for survival. In a mature healthy retina, the retinal photoreceptor outer segments interdigitate with the RPE monolayer, and they co-exchange key supportive factors. RPE cells are indispensable for the health of the retina as they are involved in a …


Mediation Of Recurrent Hypoglycemia's Physiological And Behavioral Effects In The Hippocampus By Glucocorticoids, Danielle Osborne Jan 2014

Mediation Of Recurrent Hypoglycemia's Physiological And Behavioral Effects In The Hippocampus By Glucocorticoids, Danielle Osborne

Legacy Theses & Dissertations (2009 - 2024)

Recurrent hypoglycemia (RH) occurs with the over administration of insulin resulting in severe hypoglycemia on a repetitive basis. This occurs most commonly among Type I Diabetics who rely on exogenous insulin replacement for management of their disease; however it is becoming increasingly common among Type II Diabetics. Although cognitive deficits are reported during hypoglycemia, the period following restoration of euglycemia has been denoted by improved hippocampally-mediated short-term and working memory in humans and rodents, respectively. RH is also associated with an altered glucocorticoid secretion profile in response to hypoglycemia. In vitro and in vivo approaches were utilized with the goal …


Structure-Activity Relationship Of 2,3-Benzodiazepin-4-Ones As Noncompetitive Ampa Receptor Antagonists, Mohammad Shaban Qneibi Jan 2013

Structure-Activity Relationship Of 2,3-Benzodiazepin-4-Ones As Noncompetitive Ampa Receptor Antagonists, Mohammad Shaban Qneibi

Legacy Theses & Dissertations (2009 - 2024)

2,3-Benzodiazepin-4-one (BDZ-11) derivatives are a special group of 2,3-benzodiazepine compounds. These compounds have been previously synthesized as AMPA receptor inhibitors, and they are also potential drugs for the treatment of various neurological diseases involving excessive AMPA receptor activity. AMPA receptors are a subtype of glutamate ion channel proteins and are responsible for the majority of excitatory neurotransmission in the mammalian central nervous system. Specifically, they are critically involved in neuronal development and brain activities, including learning and memory. Overstimulation of AMPA receptors is associated with some neurological diseases such as ALS, stroke and Alzheimer's disease. Despite the fact that hundreds …


Mechanism Of Inhibition Of The Glua2 Receptors By N-3 Derivatives Of 2,3-Benzodiazepines With C-4 Methyl Group, Congzhou Wang Jan 2012

Mechanism Of Inhibition Of The Glua2 Receptors By N-3 Derivatives Of 2,3-Benzodiazepines With C-4 Methyl Group, Congzhou Wang

Legacy Theses & Dissertations (2009 - 2024)

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are one of the three subtypes of ionotropic glutamate receptors. AMPA receptors mediate fast synaptic neurotransmission in the central nervous system (CNS). Over-activation of calcium permeable AMPA receptors causes intracellular calcium overload, which leads to neurodegeneration and cell death. As such, AMPA receptors have been implicated in a number of neurological disorders and diseases, such as epilepsy, amyotrophic lateral sclerosis (ALS), and Parkinson's disease. 2,3-Benzodiazepine derivatives (or GYKI compounds) are a group of structurally similar compounds synthesized as inhibitors of AMPA receptors, and they have been used as potential drug candidates for the treatment of various …