Nervous System Diseases Commons^™

Impaired Dnajb2 Response To Heat Shock In Fibroblasts From A Neuropathy Patient With Dnajb2/Hsj1 Mutation: Cystamine As A Potential Therapeutic Intervention, Raj K. Pradhan, Nikolas G. Kinney, Brigid K. Jensen, Hristelina Ilieva

Farber Institute for Neuroscience Faculty Papers

Background and Objectives: Neuropathy is a debilitating disorder characterized by peripheral nerve dysfunction and damage to sensory, motor, and autonomic neurons and their axons. While homozygous mutations in DNAJB2/HSJ1 have been linked to early-onset neuropathy, a heterozygous DNAJB2 c.823+6C>T was discovered in an adult patient with severe sensory–motor polyneuropathy. This mutation is predicted to affect both isoforms of the protein. DNAJB2 (HSP40), a key member of the heat shock protein family, plays a critical role in cellular protection and stress, including response to heat shock. DNAJB2 traffics unfolded proteins to another heat shock protein, HSP70, and activates its ATPase …

Rod Photoreceptor Regeneration In A Zebrafish Model With Retinitis Pigmentosa, Eyad Shihabeddin

Dissertations and Theses (Open Access)

A cellular hallmark of inherited retinal degenerative diseases is progressive loss of photoreceptors until one is completely blind. Unlike mammalian models, Zebrafish have the ability to naturally regenerate their neurons after injury or disease is detected. We have generated a zebrafish model with the most common autosomal dominant form of the inherited retinal degenerative disease known as Retinitis Pigmentosa. We utilize immunohistochemistry, single-cell RNA sequencing, several analysis tools, behavioral assays and oligonucleotides to characterize our zebrafish model and identify the transcription factors necessary for rod photoreceptor regeneration. We show that our zebrafish model has continuous degeneration and regeneration of rod …

Exploring The Immunologic Consequences Of Atrx Deficiency In Glioma, Benjamin Whitfield

Dissertations and Theses (Open Access)

ATRX is a key chromatin regulator that is frequently mutated across multiple cancer types. One of the most common ATRX-mutated tumor types is the adult-type glioma, IDH-mutant, Astrocytoma. It is known that ATRX mutation leads to increases in DNA damage, replication stress, and global epigenetic regulation at a cell level; however, less is known about the impact of ATRX mutation on immune signaling. Furthermore, little is known about the interaction of ATRX loss with gain-of-function mutations in IDH. In this paper we set out to explore the impact of ATRX loss on immune signaling in gliomas, both in the context …

Effect Of Chronic Alcohol Feeding Using The Lieber-Decarli Diet On Alzheimer’S Disease Pathology In Tg2576 Mice, Devaraj V. Chandrashekar, Nataraj Jagadeesan, Tamara Abdullah, Rudy Chang, Ross A. Steinberg, Frankey Sanchez, Elias Khal, Joshua Yang, David H. Cribbs, Derick Han, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background: Chronic alcohol drinking is a modifiable risk factor for Alzheimer’s disease (AD), but underlying mechanisms remain poorly understood. Most studies of alcohol feeding to AD mice have utilized young mice and delivered alcohol in drinking water without controlling nutritional intake.

Objective: To study the impact of Lieber-DeCarli (LDC) liquid alcohol diet, which balances nutritional intake, on AD pathology of aged Tg2576 and wild-type (WT) mice, which is unexplored.

Methods: 13-month-old male and female Tg2576 or WT mice were fed LDC diet (5% ethanol or control) for six weeks (n = 11-13/group). Exploration (open-field test) and spatial reference memory …

Radial Glia Integrin Avb8 Regulates Cell Autonomous Microglial Tgfβ1 Signaling That Is Necessary For Microglial Identity, Gabriel Mckinsey, Nicolas Santander, Xiaoming Zhang, Kilian Kleemann, Lauren Tran, Aditya Katewa, Kaylynn Conant, Matthew Barraza, Kian Waddell, Carlos Lizama, Marie La Russa, Ji Hyun Koo, Hyunji Lee, Dibyanti Mukherjee, Helena Paidassi, E. S. Anton, Kamran Atabai, Dean Sheppard, Oleg Butovsky, Thomas Arnold

Department of Medicine Faculty Papers

Microglial diversity arises from the interplay between inherent genetic programs and external environmental signals. However, the mechanisms by which these processes develop and interact within the growing brain are not yet fully understood. Here, we show that radial glia-expressed integrin beta 8 (ITGB8) activates microglia-expressed TGFβ1 to drive microglial development. Domain-restricted deletion of Itgb8 in these progenitors results in regionally restricted and developmentally arrested microglia that persist into adulthood. In the absence of autocrine TGFβ1 signaling, microglia adopt a similar phenotype, leading to neuromotor symptoms almost identical to Itgb8 mutant mice. In contrast, microglia lacking the canonical TGFβ signal transducers …

The Impact Of Diabetes On Neurovascular Integrity: A Special Focus On Pericytes And Endothelin-1, Mia Edgerton

MUSC Theses and Dissertations

Diabetes increases the risk of stroke and Vascular Contributions to Cognitive Impairment and Dementia (VCID). Diabetes also dysregulates the endothelin (ET) system. ET-1-mediated constriction of brain microvascular pericytes (BMVPCs) has been shown to contribute to brain hypoperfusion. However, there is a loss of BMVPCs in VCID, but underlying mechanisms of pericyte degeneration are poorly studied. ETA receptor activation can instigate phenotypical changes and cellular senescence in endothelial cells. . There is also emerging evidence that ETB receptor agonism improves outcomes in patients with cerebral ischemic stroke, but long-term effects, especially in diabetes, are unknown. Therefore, this study aimed to determine …

In-Silico Modeling And Characterization Of Kcc2 Protein Interaction With A Small Molecule Direct Agonist Identifies Potential Binding Sites For Modulating Behaviors Associated With Substances Of Abuse, William Hai Dang Ho, Alfred Amendolara, Kenyon Mitchell, Jaden Miner, Ruth Northcott, Braxton Bingham, Andrew J. Payne

Annual Research Symposium

Purpose

KCC2 is a potassium-chloride cotransporter that plays a critical role in neuronal function by regulating GABAergic signaling via chloride gradients. Maintaining this concentration gradient is crucial for balancing excitation and inhibition in the brain. While KCC2 dysregulation has been implicated in epilepsy and seizures, recent studies suggest that KCC2 inhibition results in phenotypes mirroring those seen in chronic opioid dependence. As such, increasing evidence support KCC2 being a potential therapeutic target for modulating behaviors associated with substances of abuse. Currently, only a few direct small molecule agonists against KCC2 have been reported, and no definitive active site on the …

Tdp43 Autoregulation Gives Rise To Dominant Negative Isoforms That Are Tightly Controlled By Transcriptional And Post-Translational Mechanisms, Megan M. Dykstra, Kaitlin Weskamp, Nicolás B. Gómez, Jacob Waksmacki, Elizabeth Tank, M. Rebecca Glineburg, Allison Snyder, Emile Pinarbasi, Michael Bekier, Xingli Li, Morgan R. Miller, Jen Bai, Shameena Shahzad, Neha Nedumaran, Clare Wieland, Corey Stewart, Sydney Willey, Nikolas Grotewold, Jonathon Mcbride, John J. Moran, Aditya V. Suryakumar, Michael Lucas, Peter M. Tessier, Michael Ward, Peter K. Todd, Sami J. Barmada

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation. Here, we show that sTDP43 is created as a by-product of TDP43 autoregulation and cleared by nonsense-mediated RNA decay (NMD). sTDP43-encoding transcripts that escape NMD are rapidly degraded post-translationally via the proteasome …

Nls-Binding Deficient Kapβ2 Reduces Neurotoxicity Via Selective Interaction With C9orf72-Als/Ftd Dipeptide Repeats, Kevin Kim, Amandeep Girdhar, Maria Elena Cicardi, V. Kankate, Miyuki Hayashi, Ruoyu Yang, Jenny Carey, Charlotte M Fare, James Shorter, Gino Cingolani, Davide Trotti, Lin Guo

Department of Biochemistry and Molecular Biology Faculty Papers

Arginine-rich dipeptide repeat proteins (R-DPRs) are highly toxic proteins found in patients with C9orf72-linked amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). R-DPRs can cause toxicity by disrupting the natural phase behavior of RNA-binding proteins (RBPs). Mitigating this abnormal phase behavior is, therefore, crucial to reduce R-DPR-induced toxicity. Here, we use FUS as a model RBP to investigate the mechanism of R-DPR-induced aberrant RBP phase transition. We find that this phase transition can be mitigated by Kapβ2. However, as a nuclear import receptor and phase modifier for PY-NLS-containing RBPs, the function of WT Kapβ2 could lead to undesired interaction with its …

Leveraging Clinical Standards To Improve The Translational Relevance Of Therapies For Experimental Spinal Cord Injury, Aaron L. Silverstein

Theses and Dissertations--Neuroscience

Efforts to improve treatment of spinal cord injury (SCI) often use animals to develop effective therapeutics, intending to improve the survival and the quality of life of persons with SCI. Over half of all SCIs in the United States occur at the cervical level and often cause locomotor deficits and life-threatening breathing dysfunction. Thus, my dissertation is focused on this important patient population.

After beginning with a description of translational research and surveying SCI from a clinical standpoint, I turned to describe experimental models of cervical SCI and more detailed neuroimmunological findings relevant to my work. Then, I conducted a …

Cell-Type Specific Apoe4 To Apoe2 ‘Switching’ In Astrocytes And Microglia Alters Alzheimer’S Disease Neuropathology, Lesley R. Golden

Theses and Dissertations--Physiology

Apolipoprotein E (APOE) is the strongest genetic risk factor for late-onset Alzheimer’s disease (LOAD). APOE exists in three common protein isoforms throughout the population: ApoE2 (E2), ApoE3 (E3), and ApoE4 (E4). While APOE allele frequencies and the degree of AD-associated risk vary across different ethnic groups, when compared to the ‘neutral’ and most common E3 allele, the E4 allele confers up to a 33-fold increase in Alzheimer’s Disease (AD) risk. Conversely, the neuroprotective E2 allele decreases AD risk by up to 67%. Here, we aimed to determine the therapeutic potential of cell-type specific APOE allele ‘switching’ and explore …

Effects Of High-Frequency Repetitive Transcranial Magnetic Stimulation On Impulse Control Disorders In Patients With Parkinson’S Disease On Dopamine Replacement Therapy, Katherine Muksuris

Graduate Theses, Dissertations, and Problem Reports (ETD)

Parkinson’s Disease (PD) is a debilitating neurodegenerative disorder that causes motor deficits, cognitive impairment, and depression. The mainstay treatment for motor symptoms is dopamine replacement therapy (DRT). DRT takes the form of levodopa or dopamine receptor agonists (DAs) and can be associated with impulse control disorders (ICDs). Currently, the approach to mitigating these side effects is to decrease or stop DRT, which may cause motor symptoms to return, making the management of the disorder more difficult. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation treatment for multiple disorders, including its approved use for smoking cessation. It has also shown …

Computational Approaches For Diagnosing Neurological Impairments And Restoring Functional Movement, Serhii Bahdasariants

Graduate Theses, Dissertations, and Problem Reports (ETD)

Movement is the primary means by which the nervous system converts intention into interaction with the environment. Voluntary limb motion enables standing, walking, reaching, and grasping—actions that underpin self‑care, communication, and economic participation. When diseases or injuries disrupt the pathways that couple neural commands to muscle forces—whether through cortical stroke, spinal cord injury, or peripheral nerve damage—mechanical outcomes such as weakness, loss of coordination, and ultimately reduced mobility emerge. These impairments cascade into secondary complications, increased dependence on caregivers, and diminished quality of life. Quantifying how the lesion alters the mechanics of movement is therefore essential for designing targeted interventions …

Factors Affecting Sport-Related Concussion Non-Disclosure In Women's Rugby-A Multi-Country Qualitative Analysis, Lisa Ryan, Ed Daly, Katherine Hunzinger

Department of Exercise Science Faculty Papers

Background and Objectives: Collision-sport athletes, such as rugby players, are at risk of sport-related concussion (SRC). Women are known to be at higher risk of SRC and may experience more severe and chronic symptomology than men. Knowledge of the factors that affect a player’s disclosure of their concussive symptoms could help to inform strategies to improve compliance with reporting and management of head injuries. The aim of this study was to investigate the factors that may impact women rugby players’ disclosure of a concussion. Methods: Twenty-eight adult (≥18 years of age) elite and semi-elite women rugby players from the UK …

Bile Duct Ligation-Induced Cirrhosis Does Not Alter The Blood-Brain Barrier Permeability To Sucrose In Rats, Mohammad K. Miah, Ulrich Bickel, Reza Mehvar

Pharmacy Faculty Articles and Research

Contradictory results have been reported about the effects of liver diseases on the blood-brain barrier (BBB) permeability to markers. For instance, both an increase and no change in the BBB permeability to BBB markers sodium fluorescein and Evans blue have been reported in experimental cholestasis induced by bile duct ligation (BDL) in rats. These contradictory effects might be due to inherent limitations of these markers and/or methodological issues. Here, we investigated the time course of the impact of BDL in rats on BBB permeability using a recently developed stable isotope labeled marker [¹³C]sucrose, which is expected to be …

D101n: A Unique And Ill-Understood Familial Als-Related Sod1 Mutant, Analisa Lott

Honors Program Theses and Research Projects

Background: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease, with 90% of documented cases considered sporadic and about 10% showing a hereditary link; such cases are deemed as familial ALS (fALS). Superoxide dismutase (SOD), a copper-zinc binding enzyme that protects cells from damaging free radicals, has been linked to fALS with certain toxic gain of function mutations, such as the D101N mutant. The human SOD1 D101N mutant has been shown to be associated with rapidly progressing neurodegeneration yet is less prone to aggregation than similar mutants, but its deviation from wild-type (WT) SOD1 remains misunderstood.

Objective: Although the D101N …

Defining The Peripheral Plasticity Of Nociceptive Afferents Following Spinal Cord Injury And Physical Therapy Intervention., Morgan Julianna Forston

Electronic Theses and Dissertations

The focus of this dissertation is to explore the peripheral plasticity of nociceptive afferents following spinal cord injury (SCI) and whether it is exacerbated or induced when physical therapy-based muscle stretching, a therapy we have shown to be detrimental to locomotor recovery in rodents, is implemented post-SCI. Chapter I provides a brief introduction on sensory afferents with particular emphasis on nociceptive afferents and their multifaceted role within the peripheral and central nervous systems. Chapter II describes SCI epidemiology and common sensory related complications that occur in patients as well and pharmaco- and physical therapies that are employed post-SCI. Chapter III …

Ecological And Pathological Applications Of The Heat Shock Response, Taylor Rae Stanley

Theses and Dissertations

The heat shock response (HSR) is a cytoprotective stress response pathway that regulates cellular proteostasis. The HSR is an evolutionarily conserved pathway that is essential for normal cellular functioning. Here, we explore the broad ecological and pathological impacts of the HSR. In an ecological context, we perform gene level analysis of the transcriptomes of two closely related sunfish. We found that the more invasive bluegill sunfish has gene expansions in two HSR gene families, the HSP70 family and the HSP90 family compared to the redear sunfish. These gene expansions were also observed in several other teleost fish species and were …

Association Between Polygenic Scores For Brain Structure And Alzheimer's Disease, Eunjae Lee, Faria Tavacoli, Tingwei Liu, Brittany Diaz Ruiz, Hayley Ho, Alice Lee, Jingchun Chen

Undergraduate Research Symposium Posters

Alzheimer’s disease (AD) is a progressive neurodegenerative condition and the most common type of dementia. Research has shown that volumetric changes in subcortical brain structures, which make up roughly 25% of the brain's total volume and affect many physiological functions. This research project aims to investigate the genetic association between brain structures and AD. GWAS data of eight different brain structures (ICV, accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus) were used to create polygenic scores (PGSs) in a discovery (cases/controls = 2,651/2,768) and replication dataset (cases/controls = 553/644). We utilized PRSice-2 software to generate PGSs and assess genetic correlations …

Dynamic Dysregulation Of Retrotransposons In Neurodegenerative Diseases At The Single-Cell Level\, Wankun Deng, Citu Citu, Andi Liu, Zhongming Zhao

Faculty, Staff and Student Publications

Retrotransposable elements (RTEs) are common mobile genetic elements comprising ∼42% of the human genome. RTEs play critical roles in gene regulation and function, but how they are specifically involved in complex diseases is largely unknown. Here, we investigate the cellular heterogeneity of RTEs using 12 single-cell transcriptome profiles covering three neurodegenerative diseases, Alzheimer's disease (AD), Parkinson's disease, and multiple sclerosis. We identify cell type marker RTEs in neurons, astrocytes, oligodendrocytes, and oligodendrocyte precursor cells that are related to these diseases. The differential expression analysis reveals the landscape of dysregulated RTE expression, especially L1s, in excitatory neurons of multiple neurodegenerative diseases. …

Absence Of Motor Impairments Or Pathological Changes In Tmem230 Knockout Rats, Wenjuan Zhang, Hao Peng, Daihe Yang, Guohua Song, Juan He, Yun Zhou, Cao Huang, Bo Huang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Parkinson's disease (PD), which is the second most common neurodegenerative disorder, is characterized by progressive movement impairment and loss of midbrain dopaminergic neurons in the substantia nigra. Although mutations in TMEM230 are linked to familial PD, the pathogenic mechanism underlying TMEM230-associated PD remains to be elucidated. To explore the effect of TMEM230 depletion in vivo, we created TMEM230 knockout rats using CRISPR-Cas9 technology. TMEM230 knockout rats did not exhibit any core features of PD, including impaired motor function, loss of dopaminergic neurons in the substantia nigra, or altered expression of proteins related to autophagy, the Rab family, or vesicular trafficking. …

Stress Granule Formation Helps To Mitigate Neurodegeneration, M. Rebecca Glineburg, Evrim Yildirim, Nicolas Gomez, Genesis Rodriguez, Jaclyn Pak, Xingli Li, Christopher Altheim, Jacob Waksmacki, Gerald M. Mcinerney, Sami J. Barmada, Peter K. Todd

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Cellular stress pathways that inhibit translation initiation lead to transient formation of cytoplasmic RNA/protein complexes known as stress granules. Many of the proteins found within stress granules and the dynamics of stress granule formation and dissolution are implicated in neurodegenerative disease. Whether stress granule formation is protective or harmful in neurodegenerative conditions is not known. To address this, we took advantage of the alphavirus protein nsP3, which selectively binds dimers of the central stress granule nucleator protein G3BP and markedly reduces stress granule formation without directly impacting the protein translational inhibitory pathways that trigger stress granule formation. In Drosophila and …

Epidural Stimulation For Urogenital Dysfunction In The Spinal Cord Injured Rat., Natasha Lorraine Wilkins

Electronic Theses and Dissertations

Spinal cord injury (SCI) is a devastating, life changing event that greatly impacts quality of life. SCI can have body-wide, multi-system consequences including dysfunction within the urogenital system. Challenges with the urinary system include urinary incontinence, urine retention, and detrusor-sphincter dyssynergia all of which require maintenance through the regular use of catheters. Sexual dysfunction in men, who comprise nearly 80% of the SCI population, includes erectile dysfunction, anejaculation, retrograde ejaculation, poor expulsive force during ejaculation, and poor sperm quality. The treatment for sexual function in SCI men is focused more on fertility through the collection of sperm for insemination procedures …

Investigating The Role Of Insulin-Like Signaling In Paclitaxel-Induced Nociceptive Hypersensitivity Using Drosophila Melanogaster, Sreepradha Sridharan

Dissertations and Theses (Open Access)

Paclitaxel (PTX), a chemotherapeutic that alters microtubule dynamics, is known to induce nociceptive hypersensitivity and sensory neuron damage in human patients and in Drosophila larvae. We used a modified feeding protocol to establish a genetically tractable Drosophila model of PTX-induced hypersensitivity. Larvae fed PTX exhibited hypersensitivity to thermal and mechanical stimuli. Thermal hypersensitivity was observed at low concentrations of PTX (even below 1 μM per ml of food), begins within 8 hours of PTX feeding, and did not completely resolve at the larval stage. Live imaging of peripheral thermal nociceptors showed that this hypersensitivity precedes observable neuronal damage. At low …

Genomic Data Science Approaches For Understanding Human Diseases, Snehal Shah

All Dissertations

The intricate interplay of genetic predisposition, environmental influences, and lifestyle acts as the multifactorial landscape of diseases. Understanding this complexity presents a significant challenge. Molecular insights into disease mechanisms, particularly the interactions of DNA, RNA, and proteins with environmental and lifestyle factors, have revolutionized disease diagnosis, prognosis, and treatment. High-throughput technologies, such as next-generation sequencing, generate large amounts of molecular data, holding a wealth of knowledge. These datasets unveil the roles of genes and their interactions with various factors through analysis, shedding light on previously unknown molecular mechanisms underlying disease pathogenesis. Furthermore, they facilitate the discovery of biomarkers crucial for …

Colocalization Of Odc And Amyloid Plaques In Patients With Alzheimer’S Disease And Down Syndrome, Julia S. Gielczynski

Undergraduate Theses, Capstones, and Recitals

Polyamines, and their rate-limiting enzyme ornithine decarboxylase (ODC), are crucial for many functions in the central nervous system but levels decrease with age. In neurodegenerative diseases, like Alzheimer’s Disease (AD), polyamine levels begin to increase again. Yet, there are still many unanswered questions surrounding polyamine’s possible role in AD, especially in those with Down Syndrome (DS), who also have an extra copy of the amyloid precursor protein (APP) and tend to get AD far earlier than the general population. We aim to investigate if there is colocalization between amyloid plaques and Ornithine Decarboxylase (ODC) in patients with AD and AD/DS, …

Hepatic Lrp-1 Plays An Important Role In Amyloidosis In Alzheimer's Disease Mice: Potential Role In Chronic Heavy Alcohol Feeding, Devaraj V. Chandrashekar, G. Chuli Roules, Nataraj Jagadeesan, Urvashi R. Panchal, Adenike Oyegbesan, Oghenetega E. Imiruaye, Hai Zhang, Jerome Garcia, Kamaljit Kaur, Sanda Win, Tin A. Than, Neil Kaplowitz, Moom R. Roosan, Derick Han, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Methods

Frontotemporal Dementia-Like Disease Progression Elicited By Seeded Aggregation And Spread Of Fus, Sonia Vazquez-Sanchez, Britt Tilkin, Fatima Gasset-Rosa, Sitao Zhang, Diana Piol, Melissa Mcalonis-Downes, Jonathan Artates, Noe Govea-Perez, Yana Verresen, Lin Guo, Don Cleveland, James Shorter, Sandrine Da Cruz

Department of Biochemistry and Molecular Biology Faculty Papers

RNA binding proteins have emerged as central players in the mechanisms of many neurodegenerative diseases. In particular, a proteinopathy of fused in sarcoma (FUS) is present in some instances of familial Amyotrophic lateral sclerosis (ALS) and about 10% of sporadic Frontotemporal lobar degeneration (FTLD). Here we establish that focal injection of sonicated human FUS fibrils into brains of mice in which ALS-linked mutant or wild-type human FUS replaces endogenous mouse FUS is sufficient to induce focal cytoplasmic mislocalization and aggregation of mutant and wild-type FUS which with time spreads to distal regions of the brain. Human FUS fibril-induced FUS aggregation …

Deciphering The Contribution Of Microglia To Neurodegeneration In Friedreich's Ataxia, Sydney N. Gillette

Master's Theses

Friedreich's ataxia (FRDA) is the most prevalent inherited ataxia, affecting one in every 50,000 individuals in the United States. This hereditary condition is caused by an abnormal GAA trinucleotide repeat expansion within the first intron of the frataxin gene resulting in decreased levels of the frataxin protein (FXN). Insufficient cellular frataxin levels results in iron accumulation, increased reactive oxygen species production and mitochondrial dysfunction. Tissues most heavily impacted are those most dependent on oxidative phosphorylation as an energy source and include the nervous system and muscle tissue. This is evident in the clinical phenotype which includes muscle weakness, ataxia, neurodegeneration …

Unveiling The Nexus Of Cellular Quality Control: Exploring The Interplay Between Ribosome-Associated Protein Quality Control And Mitochondrial Quality Control Pathways, Foozhan Tahmasebinia

Biological Sciences Theses and Dissertations

In eukaryotic cells, the intricate interplay between cellular quality control mechanisms is crucial for maintaining homeostasis and safeguarding the integrity of vital processes, spanning from macromolecule synthesis to the renewal of entire cellular organelles.

Disruption of these networks can lead to severe diseases such as metabolic disorders, underscoring the interconnected nature and feedback control mechanisms inherent in biological systems, including cellular quality control systems. This interconnectedness extends to the intricate communication between organelles, enabling coordinated functioning and adaptation to changing cellular conditions, particularly in response to stressors.

While the exact mechanisms governing these communications within cellular quality control systems remain …