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  1. Book ; Online: Neuronal Development and Degeneration

    Zhang, Wenbo / Fort, Patrice E. / Xu, Nan-Jie

    2020  

    Keywords Science: general issues ; Neurosciences ; neuronal development ; degeneration ; retina ; brain ; neurodegenerative disease
    Size 1 electronic resource (161 pages)
    Publisher Frontiers Media SA
    Document type Book ; Online
    Note English ; Open Access
    HBZ-ID HT021231500
    ISBN 9782889633456 ; 2889633454
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Article: Reader response: Consensus-based care recommendations for adults with myotonic dystrophy type 1.

    Brignol, Tuy Nga / Fort, Patrice E

    Neurology. Clinical practice

    2019  Volume 9, Issue 5, Page(s) 366

    Language English
    Publishing date 2019-03-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2645818-4
    ISSN 2163-0933 ; 2163-0402
    ISSN (online) 2163-0933
    ISSN 2163-0402
    DOI 10.1212/CPJ.0000000000000733
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Therapeutic Potential of α-Crystallins in Retinal Neurodegenerative Diseases.

    Phadte, Ashutosh S / Sluzala, Zachary B / Fort, Patrice E

    Antioxidants (Basel, Switzerland)

    2021  Volume 10, Issue 7

    Abstract: The chaperone and anti-apoptotic activity of α-crystallins (αA- and αB-) and their derivatives has received increasing attention due to their tremendous potential in preventing cell death. While originally known and described for their role in the lens, ... ...

    Abstract The chaperone and anti-apoptotic activity of α-crystallins (αA- and αB-) and their derivatives has received increasing attention due to their tremendous potential in preventing cell death. While originally known and described for their role in the lens, the upregulation of these proteins in cells and animal models of neurodegenerative diseases highlighted their involvement in adaptive protective responses to neurodegeneration associated stress. However, several studies also suggest that chronic neurodegenerative conditions are associated with progressive loss of function of these proteins. Thus, while external supplementation of α-crystallin shows promise, their potential as a protein-based therapeutic for the treatment of chronic neurodegenerative diseases remains ambiguous. The current review aims at assessing the current literature supporting the anti-apoptotic potential of αA- and αB-crystallins and its potential involvement in retinal neurodegenerative diseases. The review further extends into potentially modulating the chaperone and the anti-apoptotic function of α-crystallins and the use of such functionally enhanced proteins for promoting neuronal viability in retinal neurodegenerative disease.
    Language English
    Publishing date 2021-06-23
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox10071001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The innate immune system in diabetic retinopathy.

    Pan, Warren W / Lin, Feng / Fort, Patrice E

    Progress in retinal and eye research

    2021  Volume 84, Page(s) 100940

    Abstract: The prevalence of diabetes has been rising steadily in the past half-century, along with the burden of its associated complications, including diabetic retinopathy (DR). DR is currently the most common cause of vision loss in working-age adults in the ... ...

    Abstract The prevalence of diabetes has been rising steadily in the past half-century, along with the burden of its associated complications, including diabetic retinopathy (DR). DR is currently the most common cause of vision loss in working-age adults in the United States. Historically, DR has been diagnosed and classified clinically based on what is visible by fundoscopy; that is vasculature alterations. However, recent technological advances have confirmed pathology of the neuroretina prior to any detectable vascular changes. These, coupled with molecular studies, and the positive impact of anti-inflammatory therapeutics in DR patients have highlighted the central involvement of the innate immune system. Reminiscent of the systemic impact of diabetes, immune dysregulation has become increasingly identified as a key element of the pathophysiology of DR by interfering with normal homeostatic systems. This review uses the growing body of literature across various model systems to demonstrate the clear involvement of all three pillars of the immune system: immune-competent cells, mediators, and the complement system. It also demonstrates how the relative contribution of each of these requires more extensive analysis, including in human tissues over the continuum of disease progression. Finally, although this review demonstrates how the complex interactions of the immune system pose many more questions than answers, the intimately connected nature of the three pillars of the immune system may also point to possible new targets to reverse or even halt reverse retinopathy.
    MeSH term(s) Complement System Proteins ; Diabetes Mellitus ; Diabetic Retinopathy/immunology ; Humans ; Immune System ; Immunity, Innate ; United States ; Vision Disorders
    Chemical Substances Complement System Proteins (9007-36-7)
    Language English
    Publishing date 2021-01-08
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1182683-6
    ISSN 1873-1635 ; 1350-9462
    ISSN (online) 1873-1635
    ISSN 1350-9462
    DOI 10.1016/j.preteyeres.2021.100940
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Heat Shock Proteins Regulatory Role in Neurodevelopment.

    Miller, David J / Fort, Patrice E

    Frontiers in neuroscience

    2018  Volume 12, Page(s) 821

    Abstract: Heat shock proteins (Hsps) are a large family of molecular chaperones that are well-known for their roles in protein maturation, re-folding and degradation. While some Hsps are constitutively expressed in certain regions, others are rapidly upregulated ... ...

    Abstract Heat shock proteins (Hsps) are a large family of molecular chaperones that are well-known for their roles in protein maturation, re-folding and degradation. While some Hsps are constitutively expressed in certain regions, others are rapidly upregulated in the presence of stressful stimuli. Numerous stressors, including hyperthermia and hypoxia, can induce the expression of Hsps, which, in turn, interact with client proteins and co-chaperones to regulate cell growth and survival. Such interactions must be tightly regulated, especially at critical points during embryonic and postnatal development. Hsps exhibit specific patterns of expression consistent with a spatio-temporally regulated role in neurodevelopment. There is also growing evidence that Hsps may promote or inhibit neurodevelopment through specific pathways regulating cell differentiation, neurite outgrowth, cell migration, or angiogenesis. This review will examine the regulatory role that these individual chaperones may play in neurodevelopment, and will focus specifically on the signaling pathways involved in the maturation of neuronal and glial cells as well as the underlying vascular network.
    Language English
    Publishing date 2018-11-12
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2018.00821
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Evidence for Paracrine Protective Role of Exogenous αA-Crystallin in Retinal Ganglion Cells.

    Nath, Madhu / Sluzala, Zachary B / Phadte, Ashutosh S / Shan, Yang / Myers, Angela M / Fort, Patrice E

    eNeuro

    2022  Volume 9, Issue 2

    Abstract: Expression and secretion of neurotrophic factors have long been known as a key mechanism of neuroglial interaction in the central nervous system. In addition, several other intrinsic neuroprotective pathways have been described, including those involving ...

    Abstract Expression and secretion of neurotrophic factors have long been known as a key mechanism of neuroglial interaction in the central nervous system. In addition, several other intrinsic neuroprotective pathways have been described, including those involving small heat shock proteins such as α-crystallins. While initially considered as a purely intracellular mechanism, both αA-crystallins and αB-crystallins have been recently reported to be secreted by glial cells. While an anti-apoptotic effect of such secreted αA-crystallin has been suggested, its regulation and protective potential remain unclear. We recently identified residue threonine 148 (T148) and its phosphorylation as a critical regulator of αA-crystallin intrinsic neuroprotective function. In the current study, we explored how mutation of this residue affected αA-crystallin chaperone function, secretion, and paracrine protective function using primary glial and neuronal cells. After demonstrating the paracrine protective effect of αA-crystallins secreted by primary Müller glial cells (MGCs), we purified and characterized recombinant αA-crystallin proteins mutated on the T148 regulatory residue. Characterization of the biochemical properties of these mutants revealed an increased chaperone activity of the phosphomimetic T148D mutant. Consistent with this observation, we also show that exogeneous supplementation of the phosphomimetic T148D mutant protein protected primary retinal neurons from metabolic stress despite similar cellular uptake. In contrast, the nonphosphorylatable mutant was completely ineffective. Altogether, our study demonstrates the paracrine role of αA-crystallin in the central nervous system as well as the therapeutic potential of functionally enhanced αA-crystallin recombinant proteins to prevent metabolic-stress induced neurodegeneration.
    MeSH term(s) Crystallins/chemistry ; Crystallins/genetics ; Crystallins/metabolism ; Molecular Chaperones/metabolism ; Recombinant Proteins/metabolism ; Retinal Ganglion Cells/metabolism
    Chemical Substances Crystallins ; Molecular Chaperones ; Recombinant Proteins
    Language English
    Publishing date 2022-03-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2800598-3
    ISSN 2373-2822 ; 2373-2822
    ISSN (online) 2373-2822
    ISSN 2373-2822
    DOI 10.1523/ENEURO.0045-22.2022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Therapeutic Potential of α-Crystallins in Retinal Neurodegenerative Diseases

    Phadte, Ashutosh S. / Sluzala, Zachary B. / Fort, Patrice E.

    Antioxidants. 2021 June 23, v. 10, no. 7

    2021  

    Abstract: The chaperone and anti-apoptotic activity of α-crystallins (αA- and αB-) and their derivatives has received increasing attention due to their tremendous potential in preventing cell death. While originally known and described for their role in the lens, ... ...

    Abstract The chaperone and anti-apoptotic activity of α-crystallins (αA- and αB-) and their derivatives has received increasing attention due to their tremendous potential in preventing cell death. While originally known and described for their role in the lens, the upregulation of these proteins in cells and animal models of neurodegenerative diseases highlighted their involvement in adaptive protective responses to neurodegeneration associated stress. However, several studies also suggest that chronic neurodegenerative conditions are associated with progressive loss of function of these proteins. Thus, while external supplementation of α-crystallin shows promise, their potential as a protein-based therapeutic for the treatment of chronic neurodegenerative diseases remains ambiguous. The current review aims at assessing the current literature supporting the anti-apoptotic potential of αA- and αB-crystallins and its potential involvement in retinal neurodegenerative diseases. The review further extends into potentially modulating the chaperone and the anti-apoptotic function of α-crystallins and the use of such functionally enhanced proteins for promoting neuronal viability in retinal neurodegenerative disease.
    Keywords animals ; cell death ; neurodegenerative diseases ; neurons ; therapeutics ; viability
    Language English
    Dates of publication 2021-0623
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox10071001
    Database NAL-Catalogue (AGRICOLA)

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  8. Article: Editorial: Neuronal Development and Degeneration.

    Fort, Patrice E / Xu, Nan-Jie / Zhang, Wenbo

    Frontiers in genetics

    2019  Volume 10, Page(s) 1213

    Language English
    Publishing date 2019-11-22
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2606823-0
    ISSN 1664-8021
    ISSN 1664-8021
    DOI 10.3389/fgene.2019.01213
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Crystallins and neuroinflammation: The glial side of the story.

    Dulle, Jennifer E / Fort, Patrice E

    Biochimica et biophysica acta

    2016  Volume 1860, Issue 1 Pt B, Page(s) 278–286

    Abstract: Background: There is an abundance of evidence to support the association of damaging neuroinflammation and neurodegeneration across a multitude of diseases. One of the links between these pathological phenomena is the role of chaperone proteins as both ... ...

    Abstract Background: There is an abundance of evidence to support the association of damaging neuroinflammation and neurodegeneration across a multitude of diseases. One of the links between these pathological phenomena is the role of chaperone proteins as both neuroprotective and immune-regulatory agents.
    Scope of review: Chaperone proteins are highly expressed at sites of neuroinflammation both in glial cells and in the injured neurons that initiate the immune response. For this reason, the use of chaperones as treatment for various diseases associated with neuroinflammation is a highly active area of investigation. This review explores the various ways that the small heat shock protein chaperones, α-crystallins, can affect glial cell function with a specific focus on their implication in the inflammatory response associated with neurodegenerative disorders, and their potential as therapeutic treatment.
    Major conclusions: Although the mechanisms are still under investigation, a clear link has now been established between alpha-crystallins and neuroinflammation, especially through their roles in microglial and macroglial cells. Interestingly, similar to inflammation in itself, crystallins can have a beneficial or detrimental impact on the CNS based on the context and duration of the condition.
    General significance: Overall this review points out the novel roles that chaperones such as alpha-crystallins can play outside of the classical protein folding pathways, and their potential in the development of new therapies for the treatment of neuroinflammatory/neurodegenerative diseases. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease.
    MeSH term(s) Animals ; Crystallins/immunology ; Humans ; Models, Immunological ; Neurogenic Inflammation/immunology ; Neurogenic Inflammation/pathology ; Neuroglia/immunology ; Neuroglia/pathology ; Neuroimmunomodulation/immunology ; Signal Transduction/immunology
    Chemical Substances Crystallins
    Language English
    Publishing date 2016-01
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 60-7
    ISSN 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbagen.2015.05.023
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

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  10. Article ; Online: Loss of αA or αB-Crystallin Accelerates Photoreceptor Cell Death in a Mouse Model of P23H Autosomal Dominant Retinitis Pigmentosa.

    Wang, Tiantian / Yao, Jingyu / Jia, Lin / Fort, Patrice E / Zacks, David N

    International journal of molecular sciences

    2021  Volume 23, Issue 1

    Abstract: Inherited retinal degenerations (IRD) are a leading cause of visual impairment and can result from mutations in any one of a multitude of genes. Mutations in the light-sensing protein rhodopsin (RHO) is a leading cause of IRD with the most common of ... ...

    Abstract Inherited retinal degenerations (IRD) are a leading cause of visual impairment and can result from mutations in any one of a multitude of genes. Mutations in the light-sensing protein rhodopsin (RHO) is a leading cause of IRD with the most common of those being a missense mutation that results in substitution of proline-23 with histidine. This variant, also known as P23H-RHO, results in rhodopsin misfolding, initiation of endoplasmic reticulum stress, the unfolded protein response, and activation of cell death pathways. In this study, we investigate the effect of α-crystallins on photoreceptor survival in a mouse model of IRD secondary to P23H-RHO. We find that knockout of either αA- or αB-crystallin results in increased intraretinal inflammation, activation of apoptosis and necroptosis, and photoreceptor death. Our data suggest an important role for the ⍺-crystallins in regulating photoreceptor survival in the P23H-RHO mouse model of IRD.
    MeSH term(s) Animals ; Apoptosis/genetics ; Cell Death/genetics ; Crystallins/genetics ; Disease Models, Animal ; Endoplasmic Reticulum/genetics ; Endoplasmic Reticulum Stress/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mutation/genetics ; Retina/pathology ; Retinal Degeneration/genetics ; Retinal Degeneration/pathology ; Retinal Rod Photoreceptor Cells/pathology ; Retinitis Pigmentosa/genetics ; Retinitis Pigmentosa/pathology ; Rhodopsin/genetics ; Unfolded Protein Response/genetics
    Chemical Substances Crystallins ; Rhodopsin (9009-81-8)
    Language English
    Publishing date 2021-12-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23010070
    Database MEDical Literature Analysis and Retrieval System OnLINE

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