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2022

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Full-Text Articles in Medicine and Health Sciences

Block The Barf: Using A Validated Scale To Measure Nausea., Jane Choe, Lauren Maloy Jan 2022

Block The Barf: Using A Validated Scale To Measure Nausea., Jane Choe, Lauren Maloy

2021

No abstract provided.


New Yoke State Of Mind, Bethel Adekogbe Jan 2022

New Yoke State Of Mind, Bethel Adekogbe

Quill & Scope

No abstract provided.


Rocketship, Amanda Torres Jan 2022

Rocketship, Amanda Torres

Quill & Scope

No abstract provided.


When Nurse Jackson Met Dr. Walker, Karizma Chhabra Jan 2022

When Nurse Jackson Met Dr. Walker, Karizma Chhabra

Quill & Scope

No abstract provided.


Metamorphosis, Sabrina Martinez Jan 2022

Metamorphosis, Sabrina Martinez

Quill & Scope

No abstract provided.


Listen, Ariel Sasson Jan 2022

Listen, Ariel Sasson

Quill & Scope

No abstract provided.


Dignity Therapy: A Narrative Intervention For End-Of-Life Care, Maya Pandit Jan 2022

Dignity Therapy: A Narrative Intervention For End-Of-Life Care, Maya Pandit

Quill & Scope

No abstract provided.


An Interview With Dr. Ray Whitt, Md, Facog, Gillian Hecht, Brinda Raval Jan 2022

An Interview With Dr. Ray Whitt, Md, Facog, Gillian Hecht, Brinda Raval

Quill & Scope

No abstract provided.


Fiction Of A Medical Student, Aaron Rips Jan 2022

Fiction Of A Medical Student, Aaron Rips

Quill & Scope

No abstract provided.


Influence Of Social Expectations On Muscle Dysmorphia In College-Age Males Studying Exercise Science, Quinten Garver Jan 2022

Influence Of Social Expectations On Muscle Dysmorphia In College-Age Males Studying Exercise Science, Quinten Garver

Williams Honors College, Honors Research Projects

PURPOSE: To investigate the correlation between the risk of an individual developing MD and the presence of unrealistic social expectations. The research question is “How do unrealistic social expectations influence the development of muscle dysmorphia in college-age males studying exercise science?”. METHODS: An electronic survey was distributed to all exercise science students at The University of Akron. This survey was targeted exclusively at male students; any responses received by females were not analyzed. The survey consisted of 20 questions that were aimed at determining the individual’s risk of developing muscle dysmorphia and determining how likely the individual is to have …


The Expression Of Satanist Identity: Does Visible Identification Of Satanism Predict Discrimination And Depression?, Allyson Dudley Jan 2022

The Expression Of Satanist Identity: Does Visible Identification Of Satanism Predict Discrimination And Depression?, Allyson Dudley

All Graduate Theses, Dissertations, and Other Capstone Projects

The current research examines the relationship between visible expression of religion, identification within Satanism, experiences of discrimination, and depression in a sample of modern Satanists (n = 1,272). Historically, Satanism has been scrutinized as immoral and a threat to public safety. The current research attempts to challenge that viewpoint by employing culturally competent methods and understanding of modern Satanism. Findings indicate a negative relationship between expression of Satanism and discrimination, expression of Satanism and depressive symptoms, in-group ties and discrimination, and identification (in-group ties and in-group affect) and depressive symptoms. Results show a positive relationship between identification with Satanism and …


Trauma Surgeons' Perceptions Of Resuscitating Lethally Injured Patients For Organ Preservation, Allan Peetz, Marie Kuzemchak, Catherine Hammack-Aviran, Oscar D. Guillamondegui, Bradley M. Dennis, Shannon Eastham, Keith Meador, Laura Beskow, Mayur Patel Jan 2022

Trauma Surgeons' Perceptions Of Resuscitating Lethally Injured Patients For Organ Preservation, Allan Peetz, Marie Kuzemchak, Catherine Hammack-Aviran, Oscar D. Guillamondegui, Bradley M. Dennis, Shannon Eastham, Keith Meador, Laura Beskow, Mayur Patel

Law Faculty Scholarship

Background: Trauma surgeons face a challenge when deciding whether to resuscitate lethally injured patients whose organ donor status is unknown. Data suggests practice pattern variability in this setting, but little is known about why.

Materials and Methods: We conducted semi-structured interviews with trauma surgeons practicing in Level 1 or 2 trauma centers in Tennessee. Interviews focused on ethical dilemmas and resource constraints. Analysis was performed using inductive thematic analysis.

Results: Response rate was 73% (11/15). Four key themes emerged. All described resuscitating patients to buy time to collect more definitive clinical information and to identify family. Some acknowledged this served …


Addressing Choice Of Law Challenges In Multi-State Precision Medicine Research: Experts' Assessment Key Factors, Leslie E. Wolf, Erin Fuse Brown, Roxanne Greeson, Catherine Hammack-Aviran, James W. Hazel, William Rencher, Laura M. Beskow Jan 2022

Addressing Choice Of Law Challenges In Multi-State Precision Medicine Research: Experts' Assessment Key Factors, Leslie E. Wolf, Erin Fuse Brown, Roxanne Greeson, Catherine Hammack-Aviran, James W. Hazel, William Rencher, Laura M. Beskow

Law Faculty Scholarship

This article explores potential frameworks for resolving choice-of-law challenges in multi-state precision medicine research. Through expert workshops involving legal scholars and research ethics specialists, the study identifies key factors relevant to determining which state laws should apply when research spans multiple jurisdictions. Participants emphasized the importance of considering the location of research institutions, participant residence, and the site of potential harm. The discussion also examined potential solutions including federal legislation, model state laws, and centralized databases of relevant statutes. The findings highlight the complexity of legal governance in large-scale biomedical research and propose strategies to improve clarity and consistency in …


Patient Perceptions Of Resident Involvement In Surgery: A Qualitative Study Using Surgical Video, Mark M. Naguib Md, R. Thomas Day Md, Catherine Hammack-Aviran Ma, Jd, Kathleen M. Brelsford Phd, Mph, Alexander Langerman Md, Sm, Facs Jan 2022

Patient Perceptions Of Resident Involvement In Surgery: A Qualitative Study Using Surgical Video, Mark M. Naguib Md, R. Thomas Day Md, Catherine Hammack-Aviran Ma, Jd, Kathleen M. Brelsford Phd, Mph, Alexander Langerman Md, Sm, Facs

Law Faculty Scholarship

This qualitative study examines patient perceptions of surgical resident involvement in operative procedures and its implications for informed consent practices. Through semi-structured interviews with 27 adult patients at a tertiary care medical center, participants viewed a video depicting collaborative surgery between an attending physician and a resident. Prior to viewing the video, participants held divergent assumptions about the role of residents, ranging from passive observation to active procedural participation. After viewing the video, most participants expressed reassurance regarding resident involvement when it was framed as supervised teamwork. Participants emphasized the importance of transparency during the consent process, particularly regarding resident …


Self-Care: An Occupational Therapy Student Perspective, Isabelle Laposha, Stacy Smallfield Jan 2022

Self-Care: An Occupational Therapy Student Perspective, Isabelle Laposha, Stacy Smallfield

Journal Articles: Occupational Therapy

Health professional students, including occupational therapy students, report increasing rates of stress, anxiety, depression, and burnout while completing their academic programs of study. Self-care is one potential solution to this crisis, as engagement in evidence-based self-care practices has been found to improve the health and well-being of various student populations; however, the self-care practices of occupational therapy students have not been well studied. Therefore, this study explored how occupational therapy students understand and practice self-care, and how self-care correlates to perceived stress. Twenty participants engaged in a focus group and completed a 72-hour time diary. Focus group results indicated that …


Editorial: Emerging And Re-Emerging Viral Zoonoses, Naveen Kumar, Vladimir N. Uversky, Shailly Tomar, Kenneth S. M. Li, Keith Chappell, Susanna K. P. Lau Jan 2022

Editorial: Emerging And Re-Emerging Viral Zoonoses, Naveen Kumar, Vladimir N. Uversky, Shailly Tomar, Kenneth S. M. Li, Keith Chappell, Susanna K. P. Lau

Molecular Medicine Faculty Publications

No abstract provided.


An Issue Of Concern: Unique Truncated Orf8 Protein Variants Of Sars-Cov-2, Sk. Sarif Hassan, Vaishnavi Kodakandla, Elrashdy M. Redwan, Kenneth Lundstrom, Pabitra Pal Choudhury, Tarek Mohamed El-Aziz, Kazuo Takayama, Ramesh Kandimalla, Amos Lal, Ángel Serrano-Aroca, Gajendra Kumar Azad, Alaa A.A. Aljabali, Giorgio Palù, Gaurav Chauhan, Parise Adadi, Murtaza Tambuwala, Adam M. Brufsky, Wagner Baetas-Da-Cruz, Debmalya Barh, Vasco Azevedo, Nikolas G. Bazan, Bruno Silva Andrade, Raner José Silva, Vladimir N. Uversky Jan 2022

An Issue Of Concern: Unique Truncated Orf8 Protein Variants Of Sars-Cov-2, Sk. Sarif Hassan, Vaishnavi Kodakandla, Elrashdy M. Redwan, Kenneth Lundstrom, Pabitra Pal Choudhury, Tarek Mohamed El-Aziz, Kazuo Takayama, Ramesh Kandimalla, Amos Lal, Ángel Serrano-Aroca, Gajendra Kumar Azad, Alaa A.A. Aljabali, Giorgio Palù, Gaurav Chauhan, Parise Adadi, Murtaza Tambuwala, Adam M. Brufsky, Wagner Baetas-Da-Cruz, Debmalya Barh, Vasco Azevedo, Nikolas G. Bazan, Bruno Silva Andrade, Raner José Silva, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Open reading frame 8 (ORF8) shows one of the highest levels of variability among accessory proteins in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19). It was previously reported that the ORF8 protein inhibits the presentation of viral antigens by the major histocompatibility complex class I (MHC-I), which interacts with host factors involved in pulmonary inflammation. The ORF8 protein assists SARS-CoV-2 in evading immunity and plays a role in SARS-CoV-2 replication. Among many contributing mutations, Q27STOP, a mutation in the ORF8 protein, defines the B.1.1.7 lineage of SARS-CoV-2, engendering the second wave of …


Effect Of Protein–Protein Interactions On Translational Diffusion Of Spheroidal Proteins, Aleksandra M. Kusova, Aleksandr E. Sitnitsky, Vladimir N. Uversky, Yuriy F. Zuev Jan 2022

Effect Of Protein–Protein Interactions On Translational Diffusion Of Spheroidal Proteins, Aleksandra M. Kusova, Aleksandr E. Sitnitsky, Vladimir N. Uversky, Yuriy F. Zuev

Molecular Medicine Faculty Publications

One of the commonly accepted approaches to estimate protein–protein interactions (PPI) in aqueous solutions is the analysis of their translational diffusion. The present review article observes a phenomenological approach to analyze PPI effects via concentration dependencies of self- and collective translational diffusion coefficient for several spheroidal proteins derived from the pulsed field gradient NMR (PFG NMR) and dynamic light scattering (DLS), respectively. These proteins are rigid globular α-chymotrypsin (ChTr) and human serum albumin (HSA), and partly disordered α-casein (α-CN) and β-lactoglobulin (β-Lg). The PPI analysis enabled us to reveal the dominance of intermolecular repulsion at low ionic strength of solution …


An Ayurgenomics Approach: Prakriti-Based Drug Discovery And Development For Personalized Care, Zoufang Huang, Vivek P. Chavda, Rajashri Bezbaruah, Vladimir N. Uversky, Sucharitha Palagati, Aayushi B. Patel, Zhe-Sheng Chen Jan 2022

An Ayurgenomics Approach: Prakriti-Based Drug Discovery And Development For Personalized Care, Zoufang Huang, Vivek P. Chavda, Rajashri Bezbaruah, Vladimir N. Uversky, Sucharitha Palagati, Aayushi B. Patel, Zhe-Sheng Chen

Molecular Medicine Faculty Publications

Originating in ancient India, Ayurveda is an alternative medicinal approach that provides substantial evidence for a theoretical-level analysis of all aspects of life. Unlike modern medicine, Ayurveda is based upon tridoshas (Vata, pitta, and Kapha) and Prakriti. On the other hand, the research of all the genes involved at the proteomics, metabolomics, and transcriptome levels are referred to as genomics. Geoclimatic regions (deshanupatini), familial characteristics (kulanupatini), and ethnicity (jatiprasakta) have all been shown to affect phenotypic variability. The combination of genomics with Ayurveda known as ayurgenomics provided new insights into tridosha that may pave the way for precision medicine (personalized …


Msh3 Homology And Potential Recombination Link To Sars-Cov-2 Furin Cleavage Site, Balamurali K. Ambati, Akhil Varshney, Kenneth Lundstrom, Giorgio Palù, Bruce D. Uhal, Vladimir N. Uversky, Adam M. Brufsky Jan 2022

Msh3 Homology And Potential Recombination Link To Sars-Cov-2 Furin Cleavage Site, Balamurali K. Ambati, Akhil Varshney, Kenneth Lundstrom, Giorgio Palù, Bruce D. Uhal, Vladimir N. Uversky, Adam M. Brufsky

Molecular Medicine Faculty Publications

Among numerous point mutation differences between the SARS-CoV-2 and the bat RaTG13 coronavirus, only the 12-nucleotide furin cleavage site (FCS) exceeds 3 nucleotides. A BLAST search revealed that a 19 nucleotide portion of the SARS-CoV-2 genome encompassing the furin cleavage site is a 100% complementary match to a codon-optimized proprietary sequence that is the reverse complement of the human mutS homolog (MSH3). The reverse complement sequence present in SARS-CoV-2 may occur randomly but other possibilities must be considered. Recombination in an intermediate host is an unlikely explanation. Single stranded RNA viruses such as SARS-CoV-2 utilize negative strand RNA templates in …


Bmi1 Silencing Induces Mitochondrial Dysfunction In Lung Epithelial Cells Exposed To Hyperoxia, Helena Hernández-Cuervo, Ramani Soundararajan, Sahebgowda Sidramagowda Patil, Mason T. Breitzig, Matthew Alleyn, Lakshmi Galam, Richard Lockey, Vladimir N. Uversky, Narasaiah Kolliputi Jan 2022

Bmi1 Silencing Induces Mitochondrial Dysfunction In Lung Epithelial Cells Exposed To Hyperoxia, Helena Hernández-Cuervo, Ramani Soundararajan, Sahebgowda Sidramagowda Patil, Mason T. Breitzig, Matthew Alleyn, Lakshmi Galam, Richard Lockey, Vladimir N. Uversky, Narasaiah Kolliputi

Molecular Medicine Faculty Publications

Acute Lung Injury (ALI), characterized by bilateral pulmonary infiltrates that restrict gas exchange, leads to respiratory failure. It is caused by an innate immune response with white blood cell infiltration of the lungs, release of cytokines, an increase in reactive oxygen species (ROS), oxidative stress, and changes in mitochondrial function. Mitochondrial alterations, changes in respiration, ATP production and the unbalancing fusion and fission processes are key events in ALI pathogenesis and increase mitophagy. Research indicates that BMI1 (B cell-specific Moloney murine leukemia virus integration site 1), a protein of the Polycomb repressive complex 1, is a cell cycle and survival …


What Is Parvalbumin For?, Eugene A. Permyakov, Vladimir N. Uversky Jan 2022

What Is Parvalbumin For?, Eugene A. Permyakov, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Parvalbumin (PA) is a small, acidic, mostly cytosolic Ca2+-binding protein of the EF-hand superfamily. Structural and physical properties of PA are well studied but recently two highly conserved structural motifs consisting of three amino acids each (clusters I and II), which contribute to the hydrophobic core of the EF-hand domains, have been revealed. Despite several decades of studies, physiological functions of PA are still poorly known. Since no target proteins have been revealed for PA so far, it is believed that PA acts as a slow calcium buffer. Numerous experiments on various muscle systems have shown that PA accelerates the …


Structural And Functional Insights Into Cp2c Transcription Factor Complexes, Seung Han Son, Min Young Kim, Eunbi Jo, Vladimir N. Uversky, Chul Geun Kim Jan 2022

Structural And Functional Insights Into Cp2c Transcription Factor Complexes, Seung Han Son, Min Young Kim, Eunbi Jo, Vladimir N. Uversky, Chul Geun Kim

Molecular Medicine Faculty Publications

CP2c, also known as TFCP2, α-CP2, LSF, and LBP-1c, is a prototypic member of the transcription factor (TF) CP2 subfamily involved in diverse ubiquitous and tissue/stage-specific cellular processes and in human malignancies including cancer. Despite its importance, many fundamental regulatory mechanisms of CP2c are still unclear. Here, we uncover unprecedented structural and functional aspects of CP2c using DSP crosslinking and Western blot in addition to conventional methods. We found that a monomeric form of a CP2c homotetramer (tCP2c; [C4]) binds to the known CP2c-binding DNA motif (CNRG-N(5~6)-CNRG), whereas a dimeric form of a CP2c, CP2b, and PIAS1 heterohexamer ([C2B2P2]2) binds …


Shell Disorder Models Detect That Omicron Has Harder Shells With Attenuation But Is Not A Descendant Of The Wuhan-Hu-1 Sars-Cov-2, Gerard Kian-Meng Goh, A. Keith Dunker, James A. Foster, Vladimir N. Uversky Jan 2022

Shell Disorder Models Detect That Omicron Has Harder Shells With Attenuation But Is Not A Descendant Of The Wuhan-Hu-1 Sars-Cov-2, Gerard Kian-Meng Goh, A. Keith Dunker, James A. Foster, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Before the SARS-CoV-2 Omicron variant emergence, shell disorder models (SDM) suggested that an attenuated precursor from pangolins may have entered humans in 2017 or earlier. This was based on a shell disorder analysis of SARS-CoV-1/2 and pangolin-Cov-2017. The SDM suggests that Omicron is attenuated with almost identical N (inner shell) disorder as pangolin-CoV-2017 (N-PID (percentage of intrinsic disorder): 44.8% vs. 44.9%—lower than other variants). The outer shell disorder (M-PID) of Omicron is lower than that of other variants and pangolin-CoV-2017 (5.4% vs. 5.9%). COVID-19-related CoVs have the lowest M-PIDs (hardest outer shell) among all CoVs. This is likely to be …


Peptidoglycan-Free Bacterial Ghosts Confer Enhanced Protection Against Yersinia Pestis Infection, Svetlana V. Dentovskaya, Anastasia S. Vagaiskaya, Mikhail E. Platonov, Alexandra S. Trunyakova, Sergey A. Kotov, Ekaterina A. Krasil’Nikova, Galina M. Titareva, Elizaveta M. Mazurina, Tat’Yana V. Gapel’Chenkova, Rima Z. Shaikhutdinova, Sergey A. Ivanov, Tat’Yana I. Kombarova, Vladimir N. Gerasimov, Vladimir N. Uversky, Andrey P. Anisimov Jan 2022

Peptidoglycan-Free Bacterial Ghosts Confer Enhanced Protection Against Yersinia Pestis Infection, Svetlana V. Dentovskaya, Anastasia S. Vagaiskaya, Mikhail E. Platonov, Alexandra S. Trunyakova, Sergey A. Kotov, Ekaterina A. Krasil’Nikova, Galina M. Titareva, Elizaveta M. Mazurina, Tat’Yana V. Gapel’Chenkova, Rima Z. Shaikhutdinova, Sergey A. Ivanov, Tat’Yana I. Kombarova, Vladimir N. Gerasimov, Vladimir N. Uversky, Andrey P. Anisimov

Molecular Medicine Faculty Publications

To develop a modern plague vaccine, we used hypo-endotoxic Yersinia pestis bacterial ghosts (BGs) with combinations of genes encoding the bacteriophage ɸX174 lysis-mediating protein E and/or holin-endolysin systems from λ or L-413C phages. Expression of the protein E gene resulted in the BGs that retained the shape of the original bacterium. Co-expression of this gene with genes coding for holin-endolysin system of the phage L-413C caused formation of structures resembling collapsed sacs. Such structures, which have lost their rigidity, were also formed as a result of the expression of only the L-413C holin-endolysin genes. A similar holin-endolysin system from phage …


Α-Synuclein Fibrils As Penrose Machines: A Chameleon In The Gear, Francesca De Giorgi, Vladimir N. Uversky, François Ichas Jan 2022

Α-Synuclein Fibrils As Penrose Machines: A Chameleon In The Gear, Francesca De Giorgi, Vladimir N. Uversky, François Ichas

Molecular Medicine Faculty Publications

In 1957, Lionel Penrose built the first man-made self-replicating mechanical device and illustrated its function in a series of machine prototypes, prefiguring our current view of the genesis and the proliferation of amyloid fibrils. He invented and demonstrated, with the help of his son Roger, the concepts that decades later, would become the fundamentals of prion and prion-like neurobiology: nucleation, seeding and conformational templating of monomers, linear polymer elongation, fragmentation, and spread. He published his premonitory discovery in a movie he publicly presented at only two conferences in 1958, a movie we thus reproduce here. By making a 30-year-jump in …


Theater In The Self-Cleaning Cell: Intrinsically Disordered Proteins Or Protein Regions Acting With Membranes In Autophagy, Hana Popelka, Vladimir N. Uversky Jan 2022

Theater In The Self-Cleaning Cell: Intrinsically Disordered Proteins Or Protein Regions Acting With Membranes In Autophagy, Hana Popelka, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Intrinsically disordered proteins and protein regions (IDPs/IDPRs) are mainly involved in signaling pathways, where fast regulation, temporal interactions, promiscuous interactions, and assemblies of structurally diverse components including membranes are essential. The autophagy pathway builds, de novo, a membrane organelle, the autophagosome, using carefully orchestrated interactions between proteins and lipid bilayers. Here, we discuss molecular mechanisms related to the protein disorder-based interactions of the autophagy machinery with membranes. We describe not only membrane binding phenomenon, but also examples of membrane remodeling processes including membrane tethering, bending, curvature sensing, and/or fragmentation of membrane organelles such as the endoplasmic reticulum, which is an …


Arrow Of Time, Entropy, And Protein Folding: Holistic View On Biochirality, Victor V. Dyakin, Vladimir N. Uversky Jan 2022

Arrow Of Time, Entropy, And Protein Folding: Holistic View On Biochirality, Victor V. Dyakin, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Chirality is a universal phenomenon, embracing the space–time domains of non-organic and organic nature. The biological time arrow, evident in the aging of proteins and organisms, should be linked to the prevalent biomolecular chirality. This hypothesis drives our exploration of protein aging, in relation to the biological aging of an organism. Recent advances in the chirality discrimination methods and theoretical considerations of the non-equilibrium thermodynamics clarify the fundamental issues, concerning the biphasic, alternative, and stepwise changes in the conformational entropy associated with protein folding. Living cells represent open, non-equilibrium, self-organizing, and dissipative systems. The non-equilibrium thermodynamics of cell biology are …


Fundamental Clock Of Biological Aging: Convergence Of Molecular, Neurodegenerative, Cognitive And Psychiatric Pathways: Non-Equilibrium Thermodynamics Meet Psychology, Victor V. Dyakin, Nuka V. Dyakina-Fagnano, Laura B. Mcintire, Vladimir N. Uversky Jan 2022

Fundamental Clock Of Biological Aging: Convergence Of Molecular, Neurodegenerative, Cognitive And Psychiatric Pathways: Non-Equilibrium Thermodynamics Meet Psychology, Victor V. Dyakin, Nuka V. Dyakina-Fagnano, Laura B. Mcintire, Vladimir N. Uversky

Molecular Medicine Faculty Publications

In humans, age-associated degrading changes, widely observed in molecular and cellular processes underly the time-dependent decline in spatial navigation, time perception, cognitive and psychological abilities, and memory. Cross-talk of biological, cognitive, and psychological clocks provides an integrative contribution to healthy and advanced aging. At the molecular level, genome, proteome, and lipidome instability are widely recognized as the primary causal factors in aging. We narrow attention to the roles of protein aging linked to prevalent amino acids chirality, enzymatic and spontaneous (non-enzymatic) post-translational modifications (PTMs SP), and non-equilibrium phase transitions. The homochirality of protein synthesis, resulting in the steady-state non-equilibrium condition …


Ferritinophagy And Α-Synuclein: Pharmacological Targeting Of Autophagy To Restore Iron Regulation In Parkinson’S Disease, Matthew K. Boag, Angus Roberts, Vladimir N. Uversky, Linlin Ma, Des R. Richardson, Dean L. Pountney Jan 2022

Ferritinophagy And Α-Synuclein: Pharmacological Targeting Of Autophagy To Restore Iron Regulation In Parkinson’S Disease, Matthew K. Boag, Angus Roberts, Vladimir N. Uversky, Linlin Ma, Des R. Richardson, Dean L. Pountney

Molecular Medicine Faculty Publications

A major hallmark of Parkinson’s disease (PD) is the fatal destruction of dopaminergic neurons within the substantia nigra pars compacta. This event is preceded by the formation of Lewy bodies, which are cytoplasmic inclusions composed of α-synuclein protein aggregates. A triad contribution of α-synuclein aggregation, iron accumulation, and mitochondrial dysfunction plague nigral neurons, yet the events underlying iron accumulation are poorly understood. Elevated intracellular iron concentrations up-regulate ferritin expression, an iron storage protein that provides cytoprotection against redox stress. The lysosomal degradation pathway, autophagy, can release iron from ferritin stores to facilitate its trafficking in a process termed ferritinophagy. Aggregated …