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  1. Artikel ; Online: A high efficiency precision genome editing method with CRISPR in iPSCs.

    Singh, Avinash / Smedley, G Dalton / Rose, Jamee-Grace / Fredriksen, Kristina / Zhang, Ying / Li, Ling / Yuan, Shauna H

    Scientific reports

    2024  Band 14, Heft 1, Seite(n) 9933

    Abstract: The use of genetic engineering to generate point mutations in induced pluripotent stem cells (iPSCs) is essential for studying a specific genetic effect in an isogenic background. We demonstrate that a combination of p53 inhibition and pro-survival small ...

    Abstract The use of genetic engineering to generate point mutations in induced pluripotent stem cells (iPSCs) is essential for studying a specific genetic effect in an isogenic background. We demonstrate that a combination of p53 inhibition and pro-survival small molecules achieves a homologous recombination rate higher than 90% using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) in human iPSCs. Our protocol reduces the effort and time required to create isogenic lines.
    Mesh-Begriff(e) Induced Pluripotent Stem Cells/metabolism ; Induced Pluripotent Stem Cells/cytology ; Humans ; Gene Editing/methods ; CRISPR-Cas Systems ; Tumor Suppressor Protein p53/genetics ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; Homologous Recombination
    Chemische Substanzen Tumor Suppressor Protein p53
    Sprache Englisch
    Erscheinungsdatum 2024-04-30
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-024-60766-4
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: A narrative review of music therapy for neuropsychiatric symptoms in Alzheimer's disease and rationale for protocolized music teletherapy.

    Wang, Sonya G / Cevasco-Trotter, Andrea M / Silverman, Michael J / Yuan, Shauna H

    Frontiers in medicine

    2023  Band 10, Seite(n) 1248245

    Abstract: Introduction: Alzheimer's Disease (AD) constitutes a major societal problem with devastating neuropsychiatric involvement in over 90% of those diagnosed. The large spectrum of AD neuropsychiatric symptoms leads to polypharmacological prescribing that, ... ...

    Abstract Introduction: Alzheimer's Disease (AD) constitutes a major societal problem with devastating neuropsychiatric involvement in over 90% of those diagnosed. The large spectrum of AD neuropsychiatric symptoms leads to polypharmacological prescribing that, in turn, poses a major risk for increased side effects. Non-pharmacological interventions such as music therapy (MT) are therefore recommended as first-line treatments. The amalgamation of an aging population, long lifespan, and shortage of qualified music therapists limits access to MT services for AD.
    Objective: The purpose of this paper is to provide a rationale for a protocolized music teletherapy (MTT) intervention to increase accessibility for MT as a psychosocial intervention for neuropsychiatric symptoms in people with AD by conducting a narrative review of the existing MT and AD literature.
    Methods: We conducted a narrative review of MT and MTT publications indexed in PubMed and Google Scholar wherein authors used the Neuropsychiatric Inventory. We examined the impact of MT on neuropsychiatric symptoms of AD and identified MTT as a way to increase access to clinical services.
    Results: MT can have positive impacts on neuropsychiatric symptoms in AD. However, we identified an ensuing need for protocolized MT interventions, access to services, and increased awareness. MTT is an option that can address these needs.
    Discussion: Although MT can have positive effects on neuropsychiatric symptoms and can be beneficial and safe for individuals with AD, the current approach to MT practice is enormously heterogeneous with studies demonstrating variable therapist qualifications, uses of music, therapy approaches, and clinical populations. Congruently, the existing literature indicates that MT has not been standardized with protocolized interventions, making it difficult for clinicians and researchers to objectively assess the evidence, and thus, prescribe MT interventions. The lack of MT standardization, coupled with a low number of music therapists relative to people with AD, result in a lack of awareness that hinders access to MT as a psychosocial treatment for neuropsychiatric symptoms in people with AD. We therefore propose that protocolized MTT interventions are needed to increase access to better address neuropsychiatric symptoms associated with AD.
    Sprache Englisch
    Erscheinungsdatum 2023-11-21
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2023.1248245
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: The Role of PERK in Understanding Development of Neurodegenerative Diseases.

    Smedley, Garrett Dalton / Walker, Keenan E / Yuan, Shauna H

    International journal of molecular sciences

    2021  Band 22, Heft 15

    Abstract: Neurodegenerative diseases are an ever-increasing problem for the rapidly aging population. Despite this, our understanding of how these neurodegenerative diseases develop and progress, is in most cases, rudimentary. Protein kinase RNA (PKR)-like ER ... ...

    Abstract Neurodegenerative diseases are an ever-increasing problem for the rapidly aging population. Despite this, our understanding of how these neurodegenerative diseases develop and progress, is in most cases, rudimentary. Protein kinase RNA (PKR)-like ER kinase (PERK) comprises one of three unfolded protein response pathways in which cells attempt to manage cellular stress. However, because of its role in the cellular stress response and the far-reaching implications of this pathway, error within the PERK pathway has been shown to lead to a variety of pathologies. Genetic and clinical studies show a correlation between failure of the PERK pathway in neural cells and the development of neurodegeneration, but the wide array of methodology of these studies is presenting conflicting narratives about the role of PERK in these affected systems. Because of the connection between PERK and pathology, PERK has become a high value target of study for understanding neurodegenerative diseases and potentially how to treat them. Here, we present a review of the literature indexed in PubMed of the PERK pathway and some of the complexities involved in investigating the protein's role in the development of neurodegenerative diseases as well as how it may act as a target for therapeutics.
    Mesh-Begriff(e) Aged ; Aging/genetics ; Aging/metabolism ; Animals ; Disease Models, Animal ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum Stress/drug effects ; Humans ; Molecular Targeted Therapy/methods ; Neurodegenerative Diseases/drug therapy ; Neurodegenerative Diseases/genetics ; Neurodegenerative Diseases/metabolism ; Polymorphism, Single Nucleotide ; Signal Transduction/drug effects ; Signal Transduction/genetics ; Unfolded Protein Response ; eIF-2 Kinase/antagonists & inhibitors ; eIF-2 Kinase/genetics ; eIF-2 Kinase/metabolism
    Chemische Substanzen EIF2AK3 protein, human (EC 2.7.11.1) ; eIF-2 Kinase (EC 2.7.11.1)
    Sprache Englisch
    Erscheinungsdatum 2021-07-29
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22158146
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel: Alzheimer's Dementia due to Suspected CTE from Subconcussive Head Impact.

    Yuan, Shauna H / Wang, Sonya G

    Case reports in neurological medicine

    2018  Band 2018, Seite(n) 7890269

    Abstract: Chronic traumatic encephalopathy (CTE) has been receiving increasing attention due to press coverage of professional football players. The devastating sequelae of CTE compel us to aim for early diagnosis and treatment. However, by current standards, CTE ... ...

    Abstract Chronic traumatic encephalopathy (CTE) has been receiving increasing attention due to press coverage of professional football players. The devastating sequelae of CTE compel us to aim for early diagnosis and treatment. However, by current standards, CTE is challenging to diagnose. Clear clinical diagnostic criteria for CTE have not been established. Only recently, pathological diagnostic criteria have been recognized, but postmortem diagnosis is too late. Reliable biomarkers are not available. By imaging criteria, cavum septum pellucidum has been the only consistent identifiable MRI finding. Because of the imprecise nature of diagnosis based on clinical suspicion, physicians must become cognizant of the broad spectrum of presentations of CTE. With this awareness, appropriate workup can be initiated. CTE can present with early symptoms of emotional changes or late symptoms with memory decline and dementia. Here we present an unusual case of a patient with Alzheimer's disease secondary to suspected CTE that stems from subconcussive head impacts presenting with severe memory and MRI changes. Clinicians should be aware of this presentation and consider CTE in their differential diagnoses while undergoing workup of memory disorders.
    Sprache Englisch
    Erscheinungsdatum 2018-07-31
    Erscheinungsland United States
    Dokumenttyp Case Reports
    ZDB-ID 2629909-4
    ISSN 2090-6676 ; 2090-6668
    ISSN (online) 2090-6676
    ISSN 2090-6668
    DOI 10.1155/2018/7890269
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: The Role of PERK in Understanding Development of Neurodegenerative Diseases

    Garrett Dalton Smedley / Keenan E. Walker / Shauna H. Yuan

    International Journal of Molecular Sciences, Vol 22, Iss 8146, p

    2021  Band 8146

    Abstract: Neurodegenerative diseases are an ever-increasing problem for the rapidly aging population. Despite this, our understanding of how these neurodegenerative diseases develop and progress, is in most cases, rudimentary. Protein kinase RNA (PKR)-like ER ... ...

    Abstract Neurodegenerative diseases are an ever-increasing problem for the rapidly aging population. Despite this, our understanding of how these neurodegenerative diseases develop and progress, is in most cases, rudimentary. Protein kinase RNA (PKR)-like ER kinase (PERK) comprises one of three unfolded protein response pathways in which cells attempt to manage cellular stress. However, because of its role in the cellular stress response and the far-reaching implications of this pathway, error within the PERK pathway has been shown to lead to a variety of pathologies. Genetic and clinical studies show a correlation between failure of the PERK pathway in neural cells and the development of neurodegeneration, but the wide array of methodology of these studies is presenting conflicting narratives about the role of PERK in these affected systems. Because of the connection between PERK and pathology, PERK has become a high value target of study for understanding neurodegenerative diseases and potentially how to treat them. Here, we present a review of the literature indexed in PubMed of the PERK pathway and some of the complexities involved in investigating the protein’s role in the development of neurodegenerative diseases as well as how it may act as a target for therapeutics.
    Schlagwörter unfolded protein response ; endoplasmic reticulum stress ; PERK ; neurodegeneration ; tauopathy ; therapy ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Sprache Englisch
    Erscheinungsdatum 2021-07-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel: Emotional Lability as a Unique Presenting Sign of Suspected Chronic Traumatic Encephalopathy.

    Yuan, Shauna H / Wang, Sonya G

    Case reports in neurological medicine

    2018  Band 2018, Seite(n) 2621416

    Abstract: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease caused by head trauma. Diagnosis of this disease is difficult as reliable biomarkers have not been established and often this clinical entity is underappreciated with poor recognition ... ...

    Abstract Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease caused by head trauma. Diagnosis of this disease is difficult as reliable biomarkers have not been established and often this clinical entity is underappreciated with poor recognition of its clinical presentations (Lenihan and Jordan, 2015). The definitive diagnosis of CTE is determined by identification of neurofibrillary tangles in the perivascular space around the sulci in postmortem tissue (McKee et al., 2015). However, performing brain biopsies searching for neurofibrillary tangles is not a feasible option for early diagnosis. Thus, diagnosis of suspected CTE in the living has been based on clinical suspicion using proposed research criteria of clinical presentations. In addition, neuroimaging techniques have shown some promise in assisting diagnosis. Clinically, CTE is more commonly known to be associated with memory impairment and executive function disorder (Stern et al., 2013). However, here, we present two unique cases of prior professional football players where behavioral changes were the first identifying factors in clinical presentation and discuss possible neuroimaging options to help with CTE diagnosis. Because behavioral changes can be mistaken for other neuropsychological diseases, recognizing differing clinical constellations is critical to early diagnosis, early intervention, and improving patient care in suspected CTE.
    Sprache Englisch
    Erscheinungsdatum 2018-01-14
    Erscheinungsland United States
    Dokumenttyp Case Reports
    ZDB-ID 2629909-4
    ISSN 2090-6676 ; 2090-6668
    ISSN (online) 2090-6676
    ISSN 2090-6668
    DOI 10.1155/2018/2621416
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: A Case of Frontotemporal Lobar Degeneration With FUS-Positive Pathology (FTLD-FET) With Corticobasal Features and Language Deficits.

    Goodwill, Vanessa / Coughlin, David / Pizzo, Donald / Galasko, Douglas / Hansen, Lawrence A / Yuan, Shauna H / Hiniker, Annie

    Journal of neuropathology and experimental neurology

    2021  Band 80, Heft 9, Seite(n) 890–892

    Mesh-Begriff(e) Frontotemporal Dementia/diagnosis ; Frontotemporal Dementia/pathology ; Frontotemporal Lobar Degeneration/diagnosis ; Frontotemporal Lobar Degeneration/pathology ; Humans ; Language ; Male ; Middle Aged ; RNA-Binding Protein FUS/metabolism
    Chemische Substanzen FUS protein, human ; RNA-Binding Protein FUS
    Sprache Englisch
    Erscheinungsdatum 2021-05-17
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3088-0
    ISSN 1554-6578 ; 0022-3069
    ISSN (online) 1554-6578
    ISSN 0022-3069
    DOI 10.1093/jnen/nlab034
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; Online: An In Vitro Model for Studying Tau Aggregation Using Lentiviral-mediated Transduction of Human Neurons.

    Aulston, Brent / Liu, Qing / Reilly, Patrick / Yuan, Shauna H

    Journal of visualized experiments : JoVE

    2019  , Heft 147

    Abstract: Aberrant aggregation of the protein tau is pathogenically involved in a number of neurodegenerative diseases, including Alzheimer's disease (AD). Although mouse models of tauopathy have provided a valuable resource for investigating the neurotoxic ... ...

    Abstract Aberrant aggregation of the protein tau is pathogenically involved in a number of neurodegenerative diseases, including Alzheimer's disease (AD). Although mouse models of tauopathy have provided a valuable resource for investigating the neurotoxic mechanisms of aggregated tau, it is becoming increasingly apparent that, due to interspecies differences in neurophysiology, the mouse brain is unsuitable for modeling the human condition. Advances in cell culture methods have made human neuronal cultures accessible for experimental use in vitro and have aided in the development of neurotherapeutics. However, despite the adaptation of human neuronal cell cultures, in vitro models of human tauopathy are not yet widely available. This protocol describes a cellular model of tau aggregation in which human neurons are transduced with lentiviral-derived vectors that code for pathogenically mutated tau fused to a yellow fluorescent protein (YFP) reporter. Transduced cultures produce tau aggregates that stain positively for thioflavin and display markers of neurotoxicity, such as decreased axonal length and increased lysosomal volume. This procedure may be a useful and cost-effective model for studying human tauopathies.
    Mesh-Begriff(e) Alzheimer Disease/physiopathology ; Animals ; Brain/pathology ; Disease Models, Animal ; Humans ; In Vitro Techniques ; Mice ; Neurons/metabolism ; tau Proteins/metabolism
    Chemische Substanzen tau Proteins
    Sprache Englisch
    Erscheinungsdatum 2019-05-23
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
    ZDB-ID 2259946-0
    ISSN 1940-087X ; 1940-087X
    ISSN (online) 1940-087X
    ISSN 1940-087X
    DOI 10.3791/59433
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; Online: Endotype reversal as a novel strategy for screening drugs targeting familial Alzheimer's disease.

    Caldwell, Andrew B / Liu, Qing / Zhang, Can / Schroth, Gary P / Galasko, Douglas R / Rynearson, Kevin D / Tanzi, Rudolph E / Yuan, Shauna H / Wagner, Steven L / Subramaniam, Shankar

    Alzheimer's & dementia : the journal of the Alzheimer's Association

    2022  Band 18, Heft 11, Seite(n) 2117–2130

    Abstract: While amyloid-β (Aβ) plaques are considered a hallmark of Alzheimer's disease, clinical trials focused on targeting gamma secretase, an enzyme involved in aberrant Aβ peptide production, have not led to amelioration of AD symptoms or synaptic ... ...

    Abstract While amyloid-β (Aβ) plaques are considered a hallmark of Alzheimer's disease, clinical trials focused on targeting gamma secretase, an enzyme involved in aberrant Aβ peptide production, have not led to amelioration of AD symptoms or synaptic dysregulation. Screening strategies based on mechanistic, multi-omics approaches that go beyond pathological readouts can aid in the evaluation of therapeutics. Using early-onset Alzheimer's (EOFAD) disease patient lineage PSEN1
    Mesh-Begriff(e) Humans ; Alzheimer Disease/drug therapy ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Amyloid Precursor Protein Secretases/metabolism ; Amyloid beta-Protein Precursor/metabolism ; Amyloid beta-Peptides/metabolism ; Plaque, Amyloid/pathology ; Induced Pluripotent Stem Cells/metabolism
    Chemische Substanzen Amyloid Precursor Protein Secretases (EC 3.4.-) ; Amyloid beta-Protein Precursor ; Amyloid beta-Peptides
    Sprache Englisch
    Erscheinungsdatum 2022-01-27
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2211627-8
    ISSN 1552-5279 ; 1552-5260
    ISSN (online) 1552-5279
    ISSN 1552-5260
    DOI 10.1002/alz.12553
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel ; Online: Mutant Presenilin 1 Dysregulates Exosomal Proteome Cargo Produced by Human-Induced Pluripotent Stem Cell Neurons.

    Podvin, Sonia / Jones, Alexander / Liu, Qing / Aulston, Brent / Mosier, Charles / Ames, Janneca / Winston, Charisse / Lietz, Christopher B / Jiang, Zhenze / O'Donoghue, Anthony J / Ikezu, Tsuneya / Rissman, Robert A / Yuan, Shauna H / Hook, Vivian

    ACS omega

    2021  Band 6, Heft 20, Seite(n) 13033–13056

    Abstract: The accumulation and propagation of hyperphosphorylated tau (p-Tau) is a neuropathological hallmark occurring with neurodegeneration of Alzheimer's disease (AD). Extracellular vesicles, exosomes, have been shown to initiate tau propagation in the brain. ... ...

    Abstract The accumulation and propagation of hyperphosphorylated tau (p-Tau) is a neuropathological hallmark occurring with neurodegeneration of Alzheimer's disease (AD). Extracellular vesicles, exosomes, have been shown to initiate tau propagation in the brain. Notably, exosomes from human-induced pluripotent stem cell (iPSC) neurons expressing the AD familial A246E mutant form of presenilin 1 (mPS1) are capable of inducing tau deposits in the mouse brain after
    Sprache Englisch
    Erscheinungsdatum 2021-05-13
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 2470-1343
    ISSN (online) 2470-1343
    DOI 10.1021/acsomega.1c00660
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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