Soluble Amyloid Precursor Protein 770 Is Released from Inflamed Endothelial Cells and Activated Platelets

Kitazume, Shinobu; Yoshihisa, Akiomi; Yamaki, Takashi; Oikawa, Masayoshi; Tachida, Yuriko; Ogawa, Kazuko; Imamaki, Rie; Hagiwara, Yoshihiro; Kinoshita, Noriaki; Takeishi, Yasuchika; Furukawa, Koichi; Tomita, Naoki; Arai, Hiroyuki; Iwata, Nobuhisa; Saido, Takaomi C.; Yamamoto, Naomasa; Taniguchi, Naoyuki

doi:10.1074/jbc.m112.398578

Cited by 51 publications

(52 citation statements)

References 36 publications

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“…A single chain antibody fragment engineered from a catalytic V L domain degraded APP (31), highlighting the risk of interference in APP function. Intact, fulllength APP is found physiologically in two forms: the membrane-bound form and the soluble, secreted form (32,33). nIgV 2E6 did not digest the purified soluble APP substrate detectably (Fig.…”

Section: Igv 2e6 Hydrolytic Properties-recombinantmentioning

confidence: 98%

Specific Amyloid β Clearance by a Catalytic Antibody Construct

Planque

Nishiyama

Sonoda

et al. 2015

Journal of Biological Chemistry

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Background: Naturally occurring catalytic antibodies (catabodies) can hydrolyze peptide bonds. Results: A catabody engineered from innate immunity principles hydrolyzed amyloid ␤ (A␤) specifically, dissolved A␤ aggregates, and cleared brain A␤ deposits without evident toxicity. Conclusion:The catabody could potentially be developed as a therapy for Alzheimer disease. Significance: The innate catabody repertoire may be a source of useful catabodies to toxic amyloids.

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Section: Igv 2e6 Hydrolytic Properties-recombinantmentioning

confidence: 98%

Specific Amyloid β Clearance by a Catalytic Antibody Construct

Planque

Nishiyama

Sonoda

et al. 2015

Journal of Biological Chemistry

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“…Aggregations of β-amyloid in small cerebral vessels seem to decrease cerebral blood fl ow and glucose utilization, which may precipitate depression [ 18 ] . sAPP can also be released from the endothelium in conditions of cardiovascular disease [ 32 ] , and exercise training has been widely reported to improve endothelial function in animal models and in patients with cardiovascular complications such as hypertension [ 29 ] . A positive eff ect of sAPP on endothelial function can therefore not be ruled out.…”

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confidence: 99%

Resistance Training Does not have an Effect on Cognition or Related Serum Biomarkers in Nonagenarians: A Randomized Controlled Trial

et al. 2014

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The aim of this randomized controlled trial was to determine the effects of 8-week exercise-intervention on cognition and related serum biochemical markers in nonagenarians. We also studied the effects of a 4-week training cessation ('detraining') period on our study variables. Participants were randomly allocated to a standard-care (control) or intervention (exercise) group [n=20 (16 women)/group]. The intervention focused on supervised, light-to-moderate-intensity aerobic and resistance exercises (mainly leg press), and included 3 weekly sessions. Cognitive status was determined by the mini-mental state examination and geriatric depression scale. We analysed proteins with reported relation with mechanisms behind cognition changes such as serum levels of angiotensin converting enzyme, amyloid-precursor protein, epidermal growth factor, brain-derived neural factor and tumor necrosis factor. No significant change (P>0.05) in any of the variables studied was found following the exercise intervention compared with the standard-care group. Similarly, no significant changes (P>0.05) were observed following the detraining period compared with the standard-care group. Overall changes after the exercise intervention in serum biomarkers were not associated with changes in functional capacity and cognitive measures. An 8-week exercise intervention focusing on resistance exercises neither benefits cognitive function nor affects the levels of the serum proteins analysed in nonagenarians.

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“…Deletion of the glycan domain of APP as well as treatment of hippocampal neurons with tunicamycin [79] indicate that N-glycans are required for the proper axonal sorting and the secretion of APP [80]. The O-glycosylation of APP has also been reported to be important in the function of APP by several authors [81][82][83][84][85][86][87][88]. We found that APP is modified with sialylated O-glycans in brain endothelial cells and that the modified APP is preferentially cleaved and secreted [86], indicating that APP O-glycosylation regulates the APP processing.…”

Section: The Role Of Protein Glycosylation In Admentioning

confidence: 99%

Glycation vs. glycosylation: a tale of two different chemistries and biology in Alzheimer’s disease

et al. 2016

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In our previous studies, we reported that the activity of an anti-oxidant enzyme, Cu,Zn-superoxide dismutase (Cu,Zn-SOD) became decreased as the result of glycation in vitro and in vivo. Glycated Cu,Zn-SOD produces hydroxyl radicals in the presence of transition metals due to the formation of a Schiff base adduct and a subsequent Amadori product. This results in the site-specific cleavage of the molecule, followed by random fragmentation. The glycation of other anti-oxidant enzymes such as glutathione peroxidase and thioredoxin reductase results in a loss or decrease in enzyme activity under pathological conditions, resulting in oxidative stress. The inactivation of anti-oxidant enzymes induces oxidative stress in aging, diabetes and neurodegenerative disorders. It is well known that the levels of Amadori products and N(e)-(carboxylmethyl)lysine (CML) and other carbonyl compounds are increased in diabetes, a situation that will be discussed by the other authors in this special issue. We and others, reported that the glycation products accumulate in the brains of patients with Alzheimer's disease (AD) patients as well as in cerebrospinal fluid (CSF), suggesting that glycation plays a pivotal role in the development of AD. We also showed that enzymatic glycosylation is implicated in the pathogenesis of AD and that oxidative stress is also important in this process. Specific types of glycosylation reactions were found to be up- or downregulated in AD patients, and key AD-related molecules including the amyloid-precursor protein (APP), tau, and APP-cleaving enzymes were shown to be functionally modified as the result of glycosylation. These results suggest that glycation as well as glycosylation are involved in oxidative stress that is associated with aging, diabetes and neurodegenerative diseases such as AD.

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Soluble Amyloid Precursor Protein 770 Is Released from Inflamed Endothelial Cells and Activated Platelets

Cited by 51 publications

References 36 publications

Specific Amyloid β Clearance by a Catalytic Antibody Construct

Specific Amyloid β Clearance by a Catalytic Antibody Construct

Resistance Training Does not have an Effect on Cognition or Related Serum Biomarkers in Nonagenarians: A Randomized Controlled Trial

Glycation vs. glycosylation: a tale of two different chemistries and biology in Alzheimer’s disease

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