Acute Anti-Inflammatory Markers ITIH4 and AHSG in Mice Brain of a Novel Alzheimer’s Disease Model

Shi, Xiaowen; Ohta, Yasuyuki; Liu, Xia; Shang, Jingwei; Morihara, Ryuta; Nakano, Yumiko; Tian, Feng; Huang, Yong; Hishikawa, Nozomi; Yamashita, Toru

doi:10.3233/jad-181218

Cited by 28 publications

(18 citation statements)

References 32 publications

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“…In fact, a recent report suggested an important role of pericyte for maintaining cerebral circulation and pleiotrophin secretion at NVU [44]. Our previous studies also reported that the mother proteins of these peptides (FAC and PPC1I) were upregulated and AHSG was downregulated in AD model mice, which were enhanced by chronic hypoperfusion [38,45]. These previous mice reports were confirmed in human AD brain samples in the present study ( Fig.…”

Section: Discussionsupporting

confidence: 90%

“…FBC and FAC are essential coagulation materials and key contributor of AD pathology [34,35]. PPC1I is a serpin superfamily, which regulates a pivotal coagulation/neuroinflammation in damaged brain [36,37], and anti-inflammatory AHSG is regulated under control of pro-inflammatory tumor necrosis factor-␣ [38,39]. Thus, the present data strongly suggest a new pathomechanism of AD, that is not simple A␤ and tau hypotheses but are in good accordance to our recent reports that suggested a neurovascular unit (NVU) damage and a neuroinflammation/plasticity of AD brain [40][41][42][43].…”

Section: Discussionmentioning

confidence: 99%

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A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer’s Disease by Peptidome Technology

Abe

Shang

Shi

et al. 2020

JAD

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Background: Because dementia is an emerging problem in the world, biochemical markers of cerebrospinal fluid (CSF) and radio-isotopic analyses are helpful for diagnosing Alzheimer's disease (AD). Although blood sample is more feasible and plausible than CSF or radiological biomarkers for screening potential AD, measurements of serum amyloid-␤ (A␤), plasma tau, and serum antibodies for A␤ 1-42 are not yet well established. Objective: We aimed to identify a new serum biomarker to detect mild cognitive impairment (MCI) and AD in comparison to cognitively healthy control by a new peptidome technology. Methods: With only 1.5 l of serum, we examined a new target plate "BLOTCHIP ® " plus a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) to discriminate control (n = 100), MCI (n = 60), and AD (n = 99). In some subjects, cognitive Mini-Mental State Examination (MMSE) were compared to positron emission tomography (PET) with Pittsburgh compound B (PiB) and the serum probability of dementia (SPD). The mother proteins of candidate serum peptides were examined in autopsied AD brains. Results: Apart from A␤ or tau, the present study discovered a new diagnostic 4-peptides-set biomarker for discriminating control, MCI, and AD with 87% of sensitivity and 65% of specificity between control and AD (* * * p < 0.001). MMSE score was well correlated to brain A␤ deposition and to SPD of AD. The mother proteins of the four peptides were upregulated for coagulation, complement, and plasticity (three proteins), and was downregulated for anti-inflammation (one protein) in AD brains.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer’s Disease by Peptidome Technology

Abe

Shang

Shi

et al. 2020

JAD

Self Cite

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“…Inter-alpha-trypsin inhibitor was found deiminated in south polar skua plasma. It is an acute inflammatory marker [171] which functions as a protease inhibitor and is linked to a range of inflammatory responses [172], oxidative stress [173] and infection [174]. Furthermore, inter-α inhibitor proteins play roles in maintaining the resting state of neutrophils by regulating shape and reducing ROS production [175].…”

Section: Discussionmentioning

confidence: 99%

Protein Deimination and Extracellular Vesicle Profiles in Antarctic Seabirds

Phillips

Kraev

Lange

2020

Biology

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Pelagic seabirds are amongst the most threatened of all avian groups. They face a range of immunological challenges which seem destined to increase due to environmental changes in their breeding and foraging habitats, affecting prey resources and exposure to pollution and pathogens. Therefore, the identification of biomarkers for the assessment of their health status is of considerable importance. Peptidylarginine deiminases (PADs) post-translationally convert arginine into citrulline in target proteins in an irreversible manner. PAD-mediated deimination can cause structural and functional changes in target proteins, allowing for protein moonlighting in physiological and pathophysiological processes. PADs furthermore contribute to the release of extracellular vesicles (EVs), which play important roles in cellular communication. In the present study, post-translationally deiminated protein and EV profiles of plasma were assessed in eight seabird species from the Antarctic, representing two avian orders: Procellariiformes (albatrosses and petrels) and Charadriiformes (waders, auks, gulls and skuas). We report some differences between the species assessed, with the narrowest EV profiles of 50–200 nm in the northern giant petrel Macronectes halli, and the highest abundance of larger 250–500 nm EVs in the brown skua Stercorarius antarcticus. The seabird EVs were positive for phylogenetically conserved EV markers and showed characteristic EV morphology. Post-translational deimination was identified in a range of key plasma proteins critical for immune response and metabolic pathways in three of the bird species under study; the wandering albatross Diomedea exulans, south polar skua Stercorarius maccormicki and northern giant petrel. Some differences in Gene Ontology (GO) biological and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for deiminated proteins were observed between these three species. This indicates that target proteins for deimination may differ, potentially contributing to a range of physiological functions relating to metabolism and immune response, as well as to key defence mechanisms. PAD protein homologues were identified in the seabird plasma by Western blotting via cross-reaction with human PAD antibodies, at an expected 75 kDa size. This is the first study to profile EVs and to identify deiminated proteins as putative novel plasma biomarkers in Antarctic seabirds. These biomarkers may be further refined to become useful indicators of physiological and immunological status in seabirds—many of which are globally threatened.

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“…Although many of the mechanisms underlying the functional importance of IAIPs are not known, increases in IAIP expression are correlated with a diverse spectrum of pathological conditions including tissue injury and repair (Huth et al, 2015;Plaas et al, 2011;Tan, McGrouther, Day, Milner, & Bayat, 2011), and inflammation (Daveau et al, 1998;Garantziotis et al, 2007;Itoh et al, 1994;Kobayashi, 2006;Mizon, Mairie, Balduyck, Hachulla, & Mizon, 2001;Okroj et al, 2012;Seifert, Kurzinger, Hopt, & Wittel, 2013;Wakahara et al, 2005). Recent studies have also reported changes in the level of IAIPs after stroke (Kashyap et al, 2009) and Alzheimer's disease (Shi et al, 2019), suggesting that endogenous IAIPs may be integrally related to the pathogenesis of inflammatory-related brain disorders. In addition, systemic levels of IAIPs have been reported to be decreased in sepsis in neonates and adults (Chaaban et al, 2009;Degraeuwe & Nieman, 2010;Opal et al, 2007) and in necrotizing enterocolitis in neonates (Chaaban et al, 2010;Shah et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Ontogeny of inter‐alpha inhibitor protein (IAIP) expression in human brain

Kim

Monte

Hovanesian

et al. 2019

J of Neuroscience Research

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Inter‐alpha inhibitor proteins (IAIPs) are naturally occurring immunomodulatory molecules found in most tissues. We have reported ontogenic changes in the expression of IAIPs in brain during development in sheep and abundant expression of IAIPs in fetal and neonatal rodent brain in a variety of cellular types and brain regions. Although a few studies identified bikunin, light chain of IAIPs, in adult human brain, the presence of the complete endogenous IAIP protein complex has not been reported in human brain. In this study, we examined the immunohistochemical expression of endogenous IAIPs in human cerebral cortex from early in development through the neonatal period and in adults using well‐preserved postmortem brains. We examined total, nuclear, and cytoplasmic staining of endogenous IAIPs and their expression in neurofilament light polypeptide–positive neurons and glial fibrillary acidic protein (GFAP)–positive astrocytes. IAIPs were ubiquitously detected for the first time in cerebral cortical cells at 24–26, 27–28, 29–36, and 37–40 weeks of gestation and in adults. Quantitative analyses revealed that IAIPs were predominately localized in the nucleus in all age groups, but cytoplasmic IAIP expression was more abundant in adult than in the younger ages. Immunoreactivity of IAIPs was expressed in neurons and astrocytes in all age groups. In addition, IAIP co‐localization with GFAP‐positive astrocytes was more abundant in adults than in the developing brain. We conclude that IAIPs exhibit ubiquitous expression, and co‐localize with neurons and astrocytes in the developing and adult human brain suggesting a potential role for IAIPs in development and endogenous neuroprotection.

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Acute Anti-Inflammatory Markers ITIH4 and AHSG in Mice Brain of a Novel Alzheimer’s Disease Model

Cited by 28 publications

References 32 publications

A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer’s Disease by Peptidome Technology

A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer’s Disease by Peptidome Technology

Protein Deimination and Extracellular Vesicle Profiles in Antarctic Seabirds

Ontogeny of inter‐alpha inhibitor protein (IAIP) expression in human brain

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