Low Erythrocyte Levels of Proteasome and Acyl-Peptide Hydrolase (APEH) Activities in Alzheimer’s Disease: A Sign of Defective Proteostasis?

Palmieri, Gianna; Cocca, Ennio; Gogliettino, Marta; Valentino, Roberta; Ruvo, Menotti; Cristofano, Gloria; Angiolillo, Antonella; Balestrieri, Marco; Rossi, Mosè; Costanzo, Alfonso Di

doi:10.3233/jad-170389

Cited by 14 publications

(10 citation statements)

References 55 publications

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“…It was known that the deposition of A β was the chief culprit in AD. Acyl-peptide hydrolase (APEH) could remove excess A β peptide and its expression in AD brain regions rich in A β plaques was increased [35]. In summary, our result found the important aging biomarkers which possibly regulate AD.…”

Section: Resultsmentioning

confidence: 79%

The Model of Aging Acceleration Network Reveals the Correlation of Alzheimer’s Disease and Aging at System Level

Zhou

Xia

et al. 2019

BioMed Research International

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As the incidence of senile dementia continues to increase, researches on Alzheimer’s disease (AD) have become more and more important. Several studies have reported that there is a close relationship between AD and aging. Some researchers even pointed out that if we wanted to understand AD in depth, mechanisms of AD based on accelerated aging must be studied. Nowadays, machine learning techniques have been utilized to deal with large and complex profiles, thus playing an important role in disease researches (i.e., modelling biological systems, identifying key modules based on biological networks, and so on). Here, we developed an aging predictor and an AD predictor using machine learning techniques, respectively. Both aging and AD biomarkers were identified to provide insights into genes associated with AD. Besides, aging scores were calculated to reflect the aging process of brain tissues. As a result, the aging acceleration network and the aging-AD bipartite graph were constructed to delve into the relationship between AD and aging. Finally, a series of network and enrichment analyses were also conducted to gain further insights into the mechanisms of AD based on accelerated aging. In a word, our results indicated that aging may contribute to the development of AD by affecting the function of the immune system and the energy metabolism process, where the immune system may play a more prominent role in AD.

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Section: Resultsmentioning

confidence: 79%

The Model of Aging Acceleration Network Reveals the Correlation of Alzheimer’s Disease and Aging at System Level

Zhou

Xia

et al. 2019

BioMed Research International

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“…The results showing such associations will be published soon. However, it is important to mention that exo- and endopeptidase activities of APEH are decreased in blood samples of Alzheimer’s patients [ 57 ]. The relationship between chronic exposure to pesticides, cognitive impairment or neurodegenerative diseases, and the role of APEH activity as an early biomarker of this pathological progression, remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Biomonitoring of blood cholinesterases and acylpeptide hydrolase activities in rural inhabitants exposed to pesticides in the Coquimbo Region of Chile

et al. 2018

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In Chile, agriculture is a relevant economic activity and is concomitant with the use of pesticides to improve the yields. Acute intoxications of agricultural workers occur with some frequency and they must be reported to the surveillance system of the Ministry of Health. However the impacts of chronic and environmental pesticide exposure have been less studied. Among pesticides frequently used in Chile for insects control are organophosphates (OP) and carbamates (CB). They are inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). In this study we determined the pattern of both biomarkers activity in three populations with different type of chronic exposure to OP/CB: environmentally exposed (EE), occupationally exposed (OE) and a reference group (RG) without exposure. Besides this, we also measured the activity of acylpeptide hydrolase (APEH), an enzyme involved in relevant functions in the central synapses that is also expressed in erythrocytes and previously reported to be highly inhibited by some OP. A baseline measurement was done in both exposure groups and then a second measurement was done during the spraying season. The RG was measured only once at any time of the year. Our results indicate that people under chronic OP/CB exposure showed an adaptive response through an increase of basal BChE activity. During the spray season only BChE activity was decreased in the EE and OE groups (p<0.05 and p<0.01, respectively) and the higher magnitude of BChE inhibition was observed in the EE group. The analysis of the frequencies of inhibition above 30% (biological tolerance limit declared by Chilean legislation) indicated that BChE was most frequently inhibited in the EE group (53% of the individuals displayed inhibition) and AChE in the OE group (55% of the individuals displayed AChE inhibition). APEH activity showed the highest frequency of inhibition in the EE group independent of its magnitude (64%). Our results demonstrate that the rural population living nearby agricultural settings displays high levels of environmental exposure. APEH activity seems to be a sensitive biomarker for acute low-level exposure and its usefulness as a routine biomarker must to be explored in future studies. Systematic biomonitoring and health outcomes studies are necessary as well as obtaining the baseline for BChE and AChE activity levels with the aim to improve environmental and occupational health policies in Chile.

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“…Despite a constantly increasing number of studies on AARE functionality in humans and its association with diseases (Palmieri et al, 2017; Zeng et al, 2017; Marshall et al, 2019, Gogliettino et al, 2021), plant AARE enzymes are far less characterized. Moreover, the complete loss of function of this protease and its impact on physiology has not yet been reported for any organism.…”

Section: Introductionmentioning

confidence: 99%

A deeply conserved protease, acylamino acid-releasing enzyme (AARE), acts in ageing in Physcomitrella and Arabidopsis

Hoernstein

Özdemir

Gessel

et al. 2022

Preprint

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Protein oxidation results from the reaction of amino-acid side chains with reactive oxygen species (ROS) and is partly irreversible. In non-photosynthetic tissues, mitochondria are a main source of ROS, whereas plastids are the major source in photosynthetic tissues. Oxidized proteins suffer from decreased structural integrity and even loss of function, and their accumulation leads to cytotoxic aggregates. In mammals, aggregate formation correlates with aging and is linked to several age-related pathologies. Mammalian proteolytic pathways for clearance of oxidized proteins are under intensive research, while mechanistic insights into this process in plants is scarce. Acylamino acid-releasing (AARE) enzymes are ATP-independent serine proteases, presumably acting on oxidized proteins and operating in a dual exo-/endopeptidase mode. They are found in all domains of life. Here, we investigated AARE enzymes in the moss Physcomitrella and the angiosperm Arabidopsis and identified three homologous nuclear genes in Physcomitrella (PpAARE1-3) and a single nuclear gene in Arabidopsis (AtAARE). Surprisingly, we observed triple localization of the proteins AtAARE and PpAARE1 to plastids, mitochondria and the cytosol in vivo, likely conserved across the plant lineage. This represents an ATP-independent possibility for degradation of oxidized proteins in the major source organelles of ROS in plants, which is distinct to mammals. Combinatorial knockout plants and protein interaction analysis revealed specific interactions of the moss AARE isoforms and functions in progressive aging. Analysis of an AtAARE T-DNA mutant further suggests the evolutionary conservation of AARE function in age-related development.

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Low Erythrocyte Levels of Proteasome and Acyl-Peptide Hydrolase (APEH) Activities in Alzheimer’s Disease: A Sign of Defective Proteostasis?

Cited by 14 publications

References 55 publications

The Model of Aging Acceleration Network Reveals the Correlation of Alzheimer’s Disease and Aging at System Level

The Model of Aging Acceleration Network Reveals the Correlation of Alzheimer’s Disease and Aging at System Level

Biomonitoring of blood cholinesterases and acylpeptide hydrolase activities in rural inhabitants exposed to pesticides in the Coquimbo Region of Chile

A deeply conserved protease, acylamino acid-releasing enzyme (AARE), acts in ageing in Physcomitrella and Arabidopsis

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