scholarly journals EK100 and Antrodin C Improve Brain Amyloid Pathology in APP/PS1 Transgenic Mice by Promoting Microglial and Perivascular Clearance Pathways

2021 ◽  
Vol 22 (19) ◽  
pp. 10413
Author(s):  
Huey-Jen Tsay ◽  
Hui-Kang Liu ◽  
Yueh-Hsiung Kuo ◽  
Chuan-Sheng Chiu ◽  
Chih-Chiang Liang ◽  
...  
Keyword(s):  
Hippocampal Neurogenesis ◽  
Amyloid Peptide ◽  
Oxidative Enzymes ◽  
Nesting Behavior ◽  
Amyloid Deposits ◽  
Bv2 Cells ◽  
Β Amyloid Peptide ◽  
The Brain ◽  
Microglia Morphology

Alzheimer’s disease (AD) is characterized by the deposition of β-amyloid peptide (Aβ). There are currently no drugs that can successfully treat this disease. This study first explored the anti-inflammatory activity of seven components isolated from Antrodia cinnamonmea in BV2 cells and selected EK100 and antrodin C for in vivo research. APPswe/PS1dE9 mice were treated with EK100 and antrodin C for one month to evaluate the effect of these reagents on AD-like pathology by nesting behavior, immunohistochemistry, and immunoblotting. Ergosterol and ibuprofen were used as control. EK100 and antrodin C improved the nesting behavior of mice, reduced the number and burden of amyloid plaques, reduced the activation of glial cells, and promoted the perivascular deposition of Aβ in the brain of mice. EK100 and antrodin C are significantly different in activating astrocytes, regulating microglia morphology, and promoting plaque-associated microglia to express oxidative enzymes. In contrast, the effects of ibuprofen and ergosterol are relatively small. In addition, EK100 significantly improved hippocampal neurogenesis in APPswe/PS1dE9 mice. Our data indicate that EK100 and antrodin C reduce the pathology of AD by reducing amyloid deposits and promoting nesting behavior in APPswe/PS1dE9 mice through microglia and perivascular clearance, indicating that EK100 and antrodin C have the potential to be used in AD treatment.

In Vivo Aggregation of β-Amyloid Peptide Variants

2002 ◽  
Vol 71 (4) ◽  
pp. 1616-1625 ◽  
Author(s):  
David S. Fay ◽  
Amy Fluet ◽  
Carolyn J. Johnson ◽  
Christopher D. Link
Keyword(s):  
Amyloid Peptide ◽  
Β Amyloid ◽  
Β Amyloid Peptide

scholarly journals Copper stabilizes antiparallel β-sheet fibrils of the amyloid β40 (Aβ40)-Iowa variant

2020 ◽  
Vol 295 (27) ◽  
pp. 8914-8927
Author(s):  
Elliot J. Crooks ◽  
Brandon A. Irizarry ◽  
Martine Ziliox ◽  
Toru Kawakami ◽  
Tiffany Victor ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Amyloid Fibrils ◽  
Brain Parenchyma ◽  
Amyloid Peptide ◽  
Amyloid Angiopathy ◽  
Seeded Growth ◽  
Amyloid Deposits ◽  
Aβ42 Peptide ◽  
Β Sheet ◽  
The Brain

Cerebral amyloid angiopathy (CAA) is a vascular disorder that primarily involves deposition of the 40-residue–long β-amyloid peptide (Aβ40) in and along small blood vessels of the brain. CAA is often associated with Alzheimer's disease (AD), which is characterized by amyloid plaques in the brain parenchyma enriched in the Aβ42 peptide. Several recent studies have suggested a structural origin that underlies the differences between the vascular amyloid deposits in CAA and the parenchymal plaques in AD. We previously have found that amyloid fibrils in vascular amyloid contain antiparallel β-sheet, whereas previous studies by other researchers have reported parallel β-sheet in fibrils from parenchymal amyloid. Using X-ray fluorescence microscopy, here we found that copper strongly co-localizes with vascular amyloid in human sporadic CAA and familial Iowa-type CAA brains compared with control brain blood vessels lacking amyloid deposits. We show that binding of Cu(II) ions to antiparallel fibrils can block the conversion of these fibrils to the more stable parallel, in-register conformation and enhances their ability to serve as templates for seeded growth. These results provide an explanation for how thermodynamically less stable antiparallel fibrils may form amyloid in or on cerebral vessels by using Cu(II) as a structural cofactor.

scholarly journals Noggin rescues age-related stem cell loss in the brain of senescent mice with neurodegenerative pathology

2018 ◽  
Vol 115 (45) ◽  
pp. 11625-11630 ◽  
Author(s):  
María Díaz-Moreno ◽  
Tomás Armenteros ◽  
Simona Gradari ◽  
Rafael Hortigüela ◽  
Laura García-Corzo ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Late Onset ◽  
Hippocampal Neurogenesis ◽  
Bmp Signaling ◽  
In Vitro Assays ◽  
Age Related ◽  
Samp8 Mice ◽  
The Brain

Increasing age is the greatest known risk factor for the sporadic late-onset forms of neurodegenerative disorders such as Alzheimer’s disease (AD). One of the brain regions most severely affected in AD is the hippocampus, a privileged structure that contains adult neural stem cells (NSCs) with neurogenic capacity. Hippocampal neurogenesis decreases during aging and the decrease is exacerbated in AD, but the mechanistic causes underlying this progressive decline remain largely unexplored. We here investigated the effect of age on NSCs and neurogenesis by analyzing the senescence accelerated mouse prone 8 (SAMP8) strain, a nontransgenic short-lived strain that spontaneously develops a pathological profile similar to that of AD and that has been employed as a model system to study the transition from healthy aging to neurodegeneration. We show that SAMP8 mice display an accelerated loss of the NSC pool that coincides with an aberrant rise in BMP6 protein, enhanced canonical BMP signaling, and increased astroglial differentiation. In vitro assays demonstrate that BMP6 severely impairs NSC expansion and promotes NSC differentiation into postmitotic astrocytes. Blocking the dysregulation of the BMP pathway and its progliogenic effect in vivo by intracranial delivery of the antagonist Noggin restores hippocampal NSC numbers, neurogenesis, and behavior in SAMP8 mice. Thus, manipulating the local microenvironment of the NSC pool counteracts hippocampal dysfunction in pathological aging. Our results shed light on interventions that may allow taking advantage of the brain’s natural plastic capacity to enhance cognitive function in late adulthood and in chronic neurodegenerative diseases such as AD.

scholarly journals Assessment of the Bioactivity of Antibodies against β-Amyloid Peptide in vitro and in vivo

2004 ◽  
Vol 1 (4-5) ◽  
pp. 160-167 ◽  
Author(s):  
M. Hasan Mohajeri ◽  
Meret N.M. Gaugler ◽  
Julia Martinez ◽  
Jay Tracy ◽  
Hong Li ◽  
...  
Keyword(s):  
Amyloid Peptide ◽  
Β Amyloid ◽  
Β Amyloid Peptide

scholarly journals Immunological Aspects and Anti-Amyloid Strategy for Alzheimer’s Dementia

2013 ◽  
Vol 64 (4) ◽  
pp. 603-608 ◽  
Author(s):  
Rajka M. Liščić
Keyword(s):  
The Elderly ◽  
Alzheimer’S Dementia ◽  
Paper Briefly ◽  
Complement Components ◽  
Synaptic Loss ◽  
Alzheimer's Dementia ◽  
Amyloid Deposits ◽  
Presymptomatic Stage ◽  
The Brain

Abstract Alzheimer’s dementia (AD) is the most common form of dementia among the elderly, accounting for at least two-thirds of all dementia cases. It represents a costly burden, since its global prevalence is estimated at 24 million cases. Amyloid beta or Aβ plaques and neurofibrillary tangles define AD pathologically but do not fully explain it, because dementia may also be caused by inflammation resulting in neuronal, axonal synaptic loss and dysfunction. An important component of AD pathophysiology are amyloid plaques surrounded by activated microglia, cytokines, and complement components, suggesting inflammation. In the diagnosis of AD, cerebrospinal fluid markers, especially in vivo amyloid measurements, contribute to an accurate assessment of AD pathology and differential diagnosis. Aβ levels are a very good marker for the presence of amyloid deposits in the brain, while total tau and phosphorylated tau are useful for the detection of neurodegeneration. The implementation of anti-amyloid therapy and other disease-modifying interventions may have immense clinical impact if initiated at an early or presymptomatic stage of AD, before significant brain damage occurs. This paper briefly reviews the abovementioned topics and provides recommendations for future studies.

scholarly journals Mutant presenilins specifically elevate the levels of the 42 residue β-amyloid peptide in vivo: evidence for augmentation of a 42-specific γ secretase

2003 ◽  
Vol 13 (2) ◽  
pp. 159-170 ◽  
Author(s):  
Joanna L. Jankowsky ◽  
Daniel J. Fadale ◽  
Jeffrey Anderson ◽  
Guilian M. Xu ◽  
Victoria Gonzales ◽  
...  
Keyword(s):  
Amyloid Peptide ◽  
Β Amyloid ◽  
Β Amyloid Peptide

Amyloidosis

2010 ◽  
pp. 1766-1779
Author(s):  
M.B. Pepys ◽  
P.N. Hawkins
Keyword(s):  
Clinical Benefit ◽  
Clinical Condition ◽  
Amyloid Fibrils ◽  
Structure And Function ◽  
Seminal Vesicles ◽  
Amyloid Deposits ◽  
Precursor Proteins ◽  
And Function ◽  
The Brain

Amyloidosis is the clinical condition caused by extracellular deposition of amyloid in the tissues. Amyloid deposits are composed of amyloid fibrils, abnormal insoluble protein fibres formed by misfolding of their normally soluble precursors. About 30 different proteins can form clinically or pathologically significant amyloid fibrils in vivo as a result of either acquired or hereditary abnormalities. Small, focal, clinically silent amyloid deposits in the brain, heart, seminal vesicles, and joints are a universal accompaniment of ageing. However, clinically important amyloid deposits usually accumulate progressively, disrupting the structure and function of affected tissues and lead inexorably to organ failure and death. No treatment yet exists which can specifically clear amyloid deposits, but intervention which reduces the availability of the amyloid fibril precursor proteins may lead to amyloid regression with clinical benefit....

Cytokine Production and Cellular Localization in a Murine Model of Brain Inflammation

2001 ◽  
Vol 7 (S2) ◽  
pp. 1008-1009
Author(s):  
J. S. Cavallo ◽  
Q. Wu ◽  
A.M. Szczepanik ◽  
X. Ying ◽  
G.E. Ringheim
Keyword(s):  
Cellular Localization ◽  
Time Course ◽  
Drug Effects ◽  
Confocal Imaging ◽  
Brain Inflammation ◽  
Amyloid Peptide ◽  
In Vivo Model ◽  
Chemokine Production ◽  
Β Amyloid Peptide

Brain inflammation is typically involved in the pathogenesis of acute conditions such as stroke and brain trauma and in chronic neurodegenerative diseases, for instance, Alzheimer’s disease. Accordingly, a well-characterized in vivo model of brain inflammation can be a useful tool to evaluate specific drug effects focused on various inflammation targets in the pharmaceutical drug discovery process. A model of brain inflammation was induced by the injection of β-amyloid peptide (αβ) or the bacterial endotoxin lipopolysaccharide (LPS) into the lateral ventricles of CD-I mice. The time course and dose response kinetics of cytokine and chemokine production were characterized. Levels of the pro-inflammatory cytokines IL-1α, IL-1β, IL-6 and the chemokine MCP-1 were significantly increased with respect to both time and dose in the cortex and hippocampus as determined by ELISA. Immunohistochemical assays were developed to detect IL-1β to determine cellular localization of this cytokine to microglia and astrocytes. Astrocytes were labeled with antibodies to glial fibrillary acidic protein (GFAP) and microglia were labeled with F4/80 antibodies. IL-1β was localized to cell type in frozen sections using double immunofluorescence (IMF) tags and were visualized with traditional fluorescence and confocal imaging.

Cloning, expression and characterization of insulin-degrading enzyme from tomato (Solanum lycopersicum)

2008 ◽  
Vol 389 (1) ◽  
pp. 91-98 ◽  
Author(s):  
Yoann Huet ◽  
Jochen Strassner ◽  
Andreas Schaller
Keyword(s):  
Solanum Lycopersicum ◽  
Catalytic Efficiency ◽  
Biochemical Properties ◽  
Amyloid Peptide ◽  
Energy Status ◽  
Insulin Degrading Enzyme ◽  
Peptide Bonds ◽  
Degrading Enzyme ◽  
Β Amyloid Peptide

Abstract A cDNA encoding insulin-degrading enzyme (IDE) was cloned from tomato (Solanum lycopersicum) and expressed in Escherichia coli in N-terminal fusion with glutathione S-transferase. GST-SlIDE was characterized as a neutral thiol-dependent metallopeptidase with insulinase activity: the recombinant enzyme cleaved the oxidized insulin B chain at eight peptide bonds, six of which are also targets of human IDE. Despite a certain preference for proline in the vicinity of the cleavage site, synthetic peptides were cleaved at apparently stochastic positions indicating that SlIDE, similar to IDEs from other organisms, does not recognize any particular amino acid motif in the primary structure of its substrates. Under steady-state conditions, an apparent K m of 62±7 μm and a catalytic efficiency (k cat/K m) of 62±15 mm -1 s-1 were determined for Abz-SKRDPPKMQTDLY(NO3)-NH2 as the substrate. GST-SlIDE was effectively inhibited by ATP at physiological concentrations, suggesting regulation of its activity in response to the energy status of the cell. While mammalian and plant IDEs share many of their biochemical properties, this similarity does not extend to their function in vivo, because insulin and the β-amyloid peptide, well-established substrates of mammalian IDEs, as well as insulin-related signaling appear to be absent from plant systems.

Sign in / Sign up

Export Citation Format

Share Document