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Article ; Online: Cycad Genotoxin Methylazoxymethanol Disrupts the Brain Ubiquitin-Proteasome Pathway, Tau and α-Synuclein, as Reported in ALS-PDC.

Kisby, Glen E / Eriksen, Jason L / Chlebowski, Anna C / Spencer, Peter S

Journal of neuropathology and experimental neurology

2021 Volume 80, Issue 3, Page(s) 286–288

MeSH term(s)	Animals ; Humans ; Mice ; alpha-Synuclein/metabolism ; Amyotrophic Lateral Sclerosis/chemically induced ; Amyotrophic Lateral Sclerosis/metabolism ; Amyotrophic Lateral Sclerosis/pathology ; Brain/drug effects ; Brain/metabolism ; Cycas/toxicity ; Methylazoxymethanol Acetate/analogs & derivatives ; Methylazoxymethanol Acetate/isolation & purification ; Methylazoxymethanol Acetate/toxicity ; Mutagens/isolation & purification ; Mutagens/toxicity ; Parkinson Disease, Secondary/chemically induced ; Parkinson Disease, Secondary/metabolism ; Parkinson Disease, Secondary/pathology ; Proteasome Endopeptidase Complex/metabolism ; Signal Transduction/drug effects ; Signal Transduction/physiology ; Ubiquitin/metabolism
Chemical Substances	alpha-Synuclein ; methylazoxymethanol (JGG19N3YDQ) ; Methylazoxymethanol Acetate (592-62-1) ; Mutagens ; Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Ubiquitin
Language	English
Publishing date	2021-01-02
Publishing country	England
Document type	Letter ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3088-0
ISSN	1554-6578 ; 0022-3069
ISSN (online)	1554-6578
ISSN	0022-3069
DOI	10.1093/jnen/nlab006
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Article ; Online: 1-Indanone and 1,3-indandione Derivatives as Ligands for Misfolded α-Synuclein Aggregates.

Sun, Xianwei / Admane, Prasad / Starosolski, Zbigniew A / Eriksen, Jason L / Annapragada, Ananth V / Tanifum, Eric A

ChemMedChem

2021 Volume 17, Issue 2, Page(s) e202100611

Abstract: The development of imaging agents for in vivo detection of alpha-synuclein (α-syn) pathologies faces several challenges. A major gap in the field is the lack of diverse molecular scaffolds with high affinity and selectivity to α-syn fibrils for in vitro ... ...

Abstract	The development of imaging agents for in vivo detection of alpha-synuclein (α-syn) pathologies faces several challenges. A major gap in the field is the lack of diverse molecular scaffolds with high affinity and selectivity to α-syn fibrils for in vitro screening assays. Better in vitro scaffolds can instruct the discovery of better in vivo agents. We report the rational design, synthesis, and in vitro evaluation of a series of novel 1-indanone and 1,3-indandione derivatives from a Structure-Activity Relationship (SAR) study centered on some existing α-syn fibril binding ligands. Our results from fibril saturation binding experiments show that two of the lead candidates compounds 8 and 32 bind α-syn fibrils with binding constants (K
MeSH term(s)	Alzheimer Disease/drug therapy ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Dose-Response Relationship, Drug ; Drug Design ; Humans ; Indans/chemical synthesis ; Indans/chemistry ; Indans/pharmacology ; Ligands ; Molecular Structure ; Neuroprotective Agents/chemical synthesis ; Neuroprotective Agents/chemistry ; Neuroprotective Agents/pharmacology ; Protein Aggregates/drug effects ; Protein Folding/drug effects ; Structure-Activity Relationship ; alpha-Synuclein/antagonists & inhibitors ; alpha-Synuclein/metabolism
Chemical Substances	Indans ; Ligands ; Neuroprotective Agents ; Protein Aggregates ; SNCA protein, human ; alpha-Synuclein ; 1,3-indandione (4DJN7YG35G)
Language	English
Publishing date	2021-11-08
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2218496-X
ISSN	1860-7187 ; 1860-7179
ISSN (online)	1860-7187
ISSN	1860-7179
DOI	10.1002/cmdc.202100611
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Article ; Online: The enigmatic roles of microglial versus neuronal progranulin in neurological disease.

Eriksen, Jason L

Acta neuropathologica

2010 Volume 119, Issue 1, Page(s) 107–109

MeSH term(s)	Animals ; Brain/metabolism ; Frontotemporal Lobar Degeneration/genetics ; Frontotemporal Lobar Degeneration/metabolism ; Humans ; Intercellular Signaling Peptides and Proteins/genetics ; Intercellular Signaling Peptides and Proteins/metabolism ; Macrophages/metabolism ; Mice ; Microglia/metabolism ; Mutation ; Neurons/metabolism ; Spinal Cord/metabolism ; Spinal Cord Injuries/genetics ; Spinal Cord Injuries/metabolism
Chemical Substances	GRN protein, human ; Grn protein, mouse ; Intercellular Signaling Peptides and Proteins
Language	English
Publishing date	2010-01
Publishing country	Germany
Document type	Comment ; Journal Article
ZDB-ID	1079-0
ISSN	1432-0533 ; 0001-6322
ISSN (online)	1432-0533
ISSN	0001-6322
DOI	10.1007/s00401-009-0623-z
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Article ; Online: Three-Dimensional Microscopy by Milling with Ultraviolet Excitation.

Guo, Jiaming / Artur, Camille / Eriksen, Jason L / Mayerich, David

Scientific reports

2019 Volume 9, Issue 1, Page(s) 14578

Abstract: Analysis of three-dimensional biological samples is critical to understanding tissue function and the mechanisms of disease. Many chronic conditions, like neurodegenerative diseases and cancers, correlate with complex tissue changes that are difficult to ...

Abstract	Analysis of three-dimensional biological samples is critical to understanding tissue function and the mechanisms of disease. Many chronic conditions, like neurodegenerative diseases and cancers, correlate with complex tissue changes that are difficult to explore using two-dimensional histology. While three-dimensional techniques such as confocal and light-sheet microscopy are well-established, they are time consuming, require expensive instrumentation, and are limited to small tissue volumes. Three-dimensional microscopy is therefore impractical in clinical settings and often limited to core facilities at major research institutions. There would be a tremendous benefit to providing clinicians and researchers with the ability to routinely image large three-dimensional tissue volumes at cellular resolution. In this paper, we propose an imaging methodology that enables fast and inexpensive three-dimensional imaging that can be readily integrated into current histology pipelines. This method relies on block-face imaging of paraffin-embedded samples using deep-ultraviolet excitation. The imaged surface is then ablated to reveal the next tissue section for imaging. The final image stack is then aligned and reconstructed to provide tissue models that exceed the depth and resolution achievable with modern three-dimensional imaging systems.
MeSH term(s)	Animals ; Brain/diagnostic imaging ; Cerebral Cortex/diagnostic imaging ; Humans ; Image Processing, Computer-Assisted/methods ; Imaging, Three-Dimensional/methods ; Liver/diagnostic imaging ; Lung/diagnostic imaging ; Mice ; Microcirculation ; Microscopy/methods ; Microscopy, Confocal/methods ; Microscopy, Ultraviolet/methods ; Microtomy/methods ; Monte Carlo Method ; Pattern Recognition, Automated ; Ultraviolet Rays
Language	English
Publishing date	2019-10-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-50870-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Multiplex protein-specific microscopy with ultraviolet surface excitation.

Guo, Jiaming / Artur, Camille / Womack, Tasha / Eriksen, Jason L / Mayerich, David

Biomedical optics express

2019 Volume 11, Issue 1, Page(s) 99–108

Abstract: Immunohistochemical techniques, such as immunofluorescence (IF) staining, enable microscopic imaging of local protein expression within tissue samples. Molecular profiling enabled by IF is critical to understanding pathogenesis and is often involved in ... ...

Abstract	Immunohistochemical techniques, such as immunofluorescence (IF) staining, enable microscopic imaging of local protein expression within tissue samples. Molecular profiling enabled by IF is critical to understanding pathogenesis and is often involved in complex diagnoses. A recent innovation, known as
Language	English
Publishing date	2019-12-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2572216-5
ISSN	2156-7085
ISSN	2156-7085
DOI	10.1364/BOE.11.000099
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Article ; Online: A surrogate marker for very early-stage tau pathology is detectable by molecular magnetic resonance imaging.

Parekh, Parag / Mu, Qingshan / Badachhape, Andrew / Bhavane, Rohan / Srivastava, Mayank / Devkota, Laxman / Sun, Xianwei / Bhandari, Prajwal / Eriksen, Jason L / Tanifum, Eric / Ghaghada, Ketan / Annapragada, Ananth

Theranostics

2022 Volume 12, Issue 12, Page(s) 5504–5521

Abstract: The abnormal phosphorylation of tau is a necessary precursor to the formation of tau fibrils, a marker of Alzheimer's disease. We hypothesize that hyperphosphorylative conditions may result in unique cell surface markers. We identify and demonstrate the ... ...

Abstract	The abnormal phosphorylation of tau is a necessary precursor to the formation of tau fibrils, a marker of Alzheimer's disease. We hypothesize that hyperphosphorylative conditions may result in unique cell surface markers. We identify and demonstrate the utility of such surrogate markers to identify the hyperphosphorylative state.
MeSH term(s)	Alzheimer Disease/pathology ; Animals ; Biomarkers ; Disease Models, Animal ; Magnetic Resonance Imaging ; Mice ; Mice, Transgenic ; Vimentin ; tau Proteins/metabolism
Chemical Substances	Biomarkers ; Vimentin ; tau Proteins
Language	English
Publishing date	2022-07-18
Publishing country	Australia
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2592097-2
ISSN	1838-7640 ; 1838-7640
ISSN (online)	1838-7640
ISSN	1838-7640
DOI	10.7150/thno.72258
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Article: Prostacyclin Promotes Degenerative Pathology in a Model of Alzheimer's Disease.

Womack, Tasha R / Vollert, Craig T / Ohia-Nwoko, Odochi / Schmitt, Monika / Montazari, Saghi / Beckett, Tina L / Mayerich, David / Murphy, Michael Paul / Eriksen, Jason L

Frontiers in cellular neuroscience

2022 Volume 16, Page(s) 769347

Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the most common form of dementia in aged populations. A substantial amount of data demonstrates that chronic neuroinflammation can accelerate neurodegenerative pathologies. In ... ...

Abstract	Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the most common form of dementia in aged populations. A substantial amount of data demonstrates that chronic neuroinflammation can accelerate neurodegenerative pathologies. In AD, chronic neuroinflammation results in the upregulation of cyclooxygenase and increased production of prostaglandin H2, a precursor for many vasoactive prostanoids. While it is well-established that many prostaglandins can modulate the progression of neurodegenerative disorders, the role of prostacyclin (PGI2) in the brain is poorly understood. We have conducted studies to assess the effect of elevated prostacyclin biosynthesis in a mouse model of AD. Upregulated prostacyclin expression significantly worsened multiple measures associated with amyloid-β (Aβ) disease pathologies. Mice overexpressing both Aβ and PGI2 exhibited impaired learning and memory and increased anxiety-like behavior compared with non-transgenic and PGI2 control mice. PGI2 overexpression accelerated the development of Aβ accumulation in the brain and selectively increased the production of soluble Aβ
Language	English
Publishing date	2022-02-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2022.769347
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Article ; Online: Three-Dimensional Microscopy by Milling with Ultraviolet Excitation

Jiaming Guo / Camille Artur / Jason L. Eriksen / David Mayerich

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 9

Abstract: Abstract Analysis of three-dimensional biological samples is critical to understanding tissue function and the mechanisms of disease. Many chronic conditions, like neurodegenerative diseases and cancers, correlate with complex tissue changes that are ... ...

Abstract	Abstract Analysis of three-dimensional biological samples is critical to understanding tissue function and the mechanisms of disease. Many chronic conditions, like neurodegenerative diseases and cancers, correlate with complex tissue changes that are difficult to explore using two-dimensional histology. While three-dimensional techniques such as confocal and light-sheet microscopy are well-established, they are time consuming, require expensive instrumentation, and are limited to small tissue volumes. Three-dimensional microscopy is therefore impractical in clinical settings and often limited to core facilities at major research institutions. There would be a tremendous benefit to providing clinicians and researchers with the ability to routinely image large three-dimensional tissue volumes at cellular resolution. In this paper, we propose an imaging methodology that enables fast and inexpensive three-dimensional imaging that can be readily integrated into current histology pipelines. This method relies on block-face imaging of paraffin-embedded samples using deep-ultraviolet excitation. The imaged surface is then ablated to reveal the next tissue section for imaging. The final image stack is then aligned and reconstructed to provide tissue models that exceed the depth and resolution achievable with modern three-dimensional imaging systems.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2019-10-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Exercise training ameliorates cerebrovascular dysfunction in a murine model of Alzheimer's disease: role of the P2Y2 receptor and endoplasmic reticulum stress.

Hong, Junyoung / Hong, Soon-Gook / Lee, Jonghae / Park, Joon-Young / Eriksen, Jason L / Rooney, Bridgette V / Park, Yoonjung

American journal of physiology. Heart and circulatory physiology

2020 Volume 318, Issue 6, Page(s) H1559–H1569

Abstract: Cerebrovascular dysfunction is a critical risk factor for the pathogenesis of Alzheimer's disease (AD). The purinergic P2Y2 receptor and endoplasmic reticulum (ER) stress are tightly associated with vascular dysfunction and the pathogenesis of AD. ... ...

Abstract	Cerebrovascular dysfunction is a critical risk factor for the pathogenesis of Alzheimer's disease (AD). The purinergic P2Y2 receptor and endoplasmic reticulum (ER) stress are tightly associated with vascular dysfunction and the pathogenesis of AD. However, the protective effects of exercise training on P2Y2 receptor- and ER stress-associated cerebrovascular dysfunction in AD are mostly unknown. Control (C57BL/6, CON) and AD (APP/PS1dE9, AD) mice underwent treadmill exercise training (EX). 2-MeS-ATP-induced dose-dependent vasoreactivity was determined by using a pressurized posterior cerebral artery (PCA) from 10-12-mo-old mice. Human brain microvascular endothelial cells (HBMECs) were exposed to laminar shear stress (LSS) at 20 dyn/cm
MeSH term(s)	Alzheimer Disease/metabolism ; Alzheimer Disease/physiopathology ; Animals ; Brain/metabolism ; Brain/physiopathology ; Cerebrovascular Circulation/physiology ; Disease Models, Animal ; Endoplasmic Reticulum Stress/physiology ; Endothelial Cells/metabolism ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/physiopathology ; Mice ; Nitric Oxide Synthase Type III/metabolism ; Physical Conditioning, Animal/physiology ; Posterior Cerebral Artery/metabolism ; Posterior Cerebral Artery/physiopathology ; Proto-Oncogene Proteins c-akt/metabolism ; Receptors, Purinergic P2Y2/metabolism
Chemical Substances	Receptors, Purinergic P2Y2 ; Nitric Oxide Synthase Type III (EC 1.14.13.39) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2020-05-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00129.2020
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Article ; Online: Recent insights into the involvement of progranulin in frontotemporal dementia.

Sun, Li / Eriksen, Jason L

Current neuropharmacology

2011 Volume 9, Issue 4, Page(s) 632–642

Abstract: Progranulin is a widely expressed protein that is involved in the regulation of multiple biological processes, including embryogenesis, host defense, and wound repair. In the central nervous system, progranulin is constitutively expressed at modest ... ...

Abstract	Progranulin is a widely expressed protein that is involved in the regulation of multiple biological processes, including embryogenesis, host defense, and wound repair. In the central nervous system, progranulin is constitutively expressed at modest levels in neurons and microglia, but shows dramatic microglial immunoreactivity in degenerative diseases that exhibit prominent neuroinflammation. In addition to the role that PGRN plays in the periphery, its expression is of critical importance in brain health, as demonstrated by recent discovery that progranulin haploinsufficiency results in familial frontotemporal lobar degeneration. Since progranulin deficiency was first described, there has been an intense ongoing effort to decipher the mysterious role that this protein plays in dementia. This review provides an update on our understanding of the possible neuronal function and discusses the challenging problems related to progranulin expression within genetics, cell biology, and neurodegeneration.
Language	English
Publishing date	2011-03-22
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	2192352-8
ISSN	1875-6190 ; 1570-159X
ISSN (online)	1875-6190
ISSN	1570-159X
DOI	10.2174/157015911798376361
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