Biochemistry Commons^™

Granulins In Norm And Neurodegenerative Pathologies, Anukool Bhopatkar

Dissertations

Granulins (GRNs) are small, cysteine-rich modules produced from the proteolytic cleavage of the precursor protein called progranulin (PGRN). GRNs are present in the form of seven tandem repeats within the precursor and are known to be produced in the extracellular and in lysosomal environments. In physiology, PGRN and GRNs plays pleiotropic roles such as neuronal growth and differentiation, immunomodulation, wound healing. Recent studies have implicated pathological role for PGRN in Alzheimer disease (AD) and frontotemporal dementia (FTD) but specific mechanism(s) remains unclear. However, potential interactions between GRNs and Ab42 and TDP-43 seem like a plausible underlying mechanism. Studies presented here …

Deciphering The Role Of Hsp110 Chaperones In Diseases Of Protein Misfolding, Unekwu M. Yakubu

Dissertations & Theses (Open Access)

Molecular chaperones maintain protein homeostasis (proteostasis) by ensuring the proper folding of polypeptides. Loss of proteostasis has been linked to the onset of numerous neurodegenerative disorders including Alzheimer’s, Parkinson’s, and Huntington’s disease. Hsp110 is a member of the Hsp70 class of molecular chaperones and acts as a nucleotide exchange factor (NEF) for Hsp70, the preeminent Hsp70-family protein folding chaperone. Hsp110 promotes rapid cycling of ADP for ATP, allowing Hsp70 to properly fold nascent or unfolded polypeptides in iterative cycles. In addition to its NEF activity, Hsp110 possesses an Hsp70-like substrate binding domain (SBD) whose biological roles are undefined. Previous work …

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 …

Semaphorin-Induced Plasticity In The Nervous System Of The Cricket, Gryllus Bimaculatus, Alicia G. Edwards

Honors Projects

The adult auditory system of the cricket, Gryllus bimaculatus, exhibits a rare example of neuronal plasticity. Upon deafferentation, we observe medial dendrites that normally respect the midline of the PTG in the central nervous system sprouting across the boundary and forming synaptic connections with the contralateral auditory afferents. The Horch Lab has investigated key molecular factors that might play a causal role in this paradigm. Specifically, the protein Sema1a.2 comes from a guidance molecule family and has a role in developmental neuronal plasticity in other organisms. In this study, I explored the role of Sema1a.2 in the neuronal plasticity of …

Photoreceptor Phosphodiesterase (Pde6): Structure, Regulatory Mechanisms, And Implications For Treatment Of Retinal Diseases, Rick H. Cote, Richa Gupta, Michael J. Irwin, Xin Wang

Faculty Publications

The photoreceptor phosphodiesterase (PDE6) is a member of large family of Class I phosphodiesterases responsible for hydrolyzing the second messengers cAMP and cGMP. PDE6 consists of two catalytic subunits and two inhibitory subunits that form a tetrameric protein. PDE6 is a peripheral membrane protein that is localized to the signaling-transducing compartment of rod and cone photoreceptors. As the central effector enzyme of the G-protein coupled visual transduction pathway, activation of PDE6 catalysis causes in a rapid decrease in cGMP levels that results in closure of cGMP-gated ion channels in the photoreceptor plasma membrane. Because of its importance in the phototransduction …

The Effects Of Rolipram, A Selective Phosphodiesterase Inhibitor, On Immortalized Schwann Cell Proliferation, Akap95 And Cyclin D3 Expression, Kyle P. Kenney, Mary Pistack, Angela Asirvatham

Student Research Poster Presentations 2021

Schwann cells are a vital component of the Peripheral Nervous System and aid in the repair of axons following injury. The regulation of Schwann cell growth in vitro is facilitated by heregulin, a neuron-secreted growth factor, and an unknown mitogen that activates the cyclic adenosine monophosphate (cAMP) pathway. The abundance of intracellular cAMP is regulated by a family of enzymes called phosphodiesterases (PDEs). PDE inhibitors such as rolipram have therapeutic potential in various disorders and function by increasing the levels of intracellular cAMP. A-Kinase anchoring proteins (AKAPs), a family of scaffolding proteins that belong to the cAMP/Protein Kinase A (PKA) …

Photoreceptor Phosphodiesterase (Pde6): Activation And Inactivation Mechanisms During Visual Transduction In Rods And Cones, Rick H. Cote

Faculty Publications

Rod and cone photoreceptors of the vertebrate retina utilize cGMP as the primary

intracellular messenger for the visual signaling pathway that converts a light stimulus into an electrical response. cGMP metabolism in the signal-transducing photoreceptor outer segment reflects the balance of cGMP synthesis (catalyzed by guanylyl cyclase) and degradation (catalyzed by the photoreceptor phosphodiesterase, PDE6). Upon light stimulation, rapid activation of PDE6 by the heterotrimeric G-protein (transducin) triggers a dramatic drop in cGMP levels that lead to cell hyperpolarization. Following cessation of the light stimulus, the lifetime of activated PDE6 is also precisely regulated by additional processes. This review summarizes …

The Receptor Basis Of Serotonergic Modulation In An Olfactory Network, Tyler Ryan Sizemore

Graduate Theses, Dissertations, and Problem Reports

Neuromodulation is a nearly ubiquitous process that endows the nervous system with the capacity to alter neural function at every level (synaptic, circuit, network, etc.) without necessarily adding new neurons. Through the actions of neuromodulators, the existing neural circuitry can be adaptively tuned to achieve flexible network output and similarly dynamic behavioral output. However, despite their near ubiquity in all sensory modalities, the mechanisms underlying neuromodulation of sensory processing remain poorly understood. In this dissertation, I address three main questions regarding the mechanisms of one modulator (serotonin) within one sensory modality (olfaction). I begin by establishing a "functional atlas" of …