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Full-Text Articles in Biochemistry

Granulins In Norm And Neurodegenerative Pathologies, Anukool Bhopatkar Dec 2021

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 Dec 2021

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 …


Determining The Role Of Methylglyoxal (Mgo) And The Trpa1 Channel In Inducing Astrocyte Senescence And Neurodegeneration, Natalie Hill May 2021

Determining The Role Of Methylglyoxal (Mgo) And The Trpa1 Channel In Inducing Astrocyte Senescence And Neurodegeneration, Natalie Hill

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Aging is the largest risk factor for the development of Alzheimer’s disease (AD) and related dementias. A recently proposed driver of age-related pathologies is cellular senescence, a phenotype that consists of cell-cycle arrest and an inflammatory response known as the senescence-associated secretory phenotype (SASP). Although there is a link between the accumulation of senescent cells and neurodegeneration, much remains unknown about how senescent cells arise in the brain. Astrocytes are the most abundant cell type in the brain that serve important roles like supporting neurons and proliferating in response to stress. Methylglyoxal (MGO) is a glycolytic byproduct that can react …


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 …


Semaphorin-Induced Plasticity In The Nervous System Of The Cricket, Gryllus Bimaculatus, Alicia G. Edwards Jan 2021

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 …


The Receptor Basis Of Serotonergic Modulation In An Olfactory Network, Tyler Ryan Sizemore Jan 2021

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 …