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Antioxidants
Special Issues
Paraoxonase-1 and Other HDL Accessory Proteins in Neurological Diseases
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Paraoxonase-1 and Other HDL Accessory Proteins in Neurological Diseases

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Aberrant Oxidation of Biomolecules".

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 17069

Special Issue Editors

Dr. Carlo Cervellati

E-Mail Website
Guest Editor
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy
Interests: oxidative stress; inflammation; HDL dysfuntion; disease biomarkers; Alzheimer’s disease; metabolic disorders; myeloperoxidase; PON-1
Special Issues, Collections and Topics in MDPI journals
Dr. Judit Marsillach

E-Mail Website
Co-Guest Editor
Department of Environmental & Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA
Interests: paraoxonases; oxidative stress; inflammation; adductomics; environmental exposures; neurodegenerative diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Substantial evidence suggests that oxidative stress (OxS) is a key player in the pathogenesis of several neurological diseases, including Alzheimer’s disease (AD), vascular dementia (VD), and multiple sclerosis. Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme that endows its carrier with multiple biological functions, including the ability to contrast oxidative damage, protect from toxicity of specific organophosphorus pesticides, and stimulate cholesterol efflux from macrophages. The impact of PON1 on HDL function relies on finely tuned coordination with apoliproteins, primarily Apoliprotein A1 (Apo A1), and other (putative) accessory proteins, such as myeloperoxidase (MPO), platelet-activating factor-acetylhydrolase, or serum amyloid A. OxS and triggered inflammation modify the HDL proteome and lipidome, leading to a dysfunctional HDL that has reduced antioxidant PON1 and accumulates pro-oxidative MPO, giving rise to a self-perpetuating detrimental cycle. This phenomenon appears to be critical in pathological processes and vascular diseases, which are well-established risk factors for CNS disorder, such as AD and VD.

This research topic will discuss experimental and epidemiological evidence giving meaningful insight into the role of PON1 and other HDL accessory proteins in the onset/progression of neurological disorders.

Dr. Carlo Cervellati
Dr. Judit Marsillach
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Paraoxonases
  • High-density lipoproteins
  • Neurological diseases
  • Aploprotein A1
  • Platelet-activating factor-acetylhydrolase
  • Myeloperoxidase

Published Papers (6 papers)

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Editorial

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4 pages, 202 KiB  
Editorial
Paraoxonase-1 and Other HDL Accessory Proteins in Neurological Diseases
by Judit Marsillach and Carlo Cervellati
Antioxidants 2021, 10(3), 454; https://doi.org/10.3390/antiox10030454 - 15 Mar 2021
Cited by 2 | Viewed by 1312
Abstract
The burden of neurological diseases continues to increase as they still are the leading cause of disability and the second-leading cause of death worldwide [...] Full article
(This article belongs to the Special Issue Paraoxonase-1 and Other HDL Accessory Proteins in Neurological Diseases)

Research

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11 pages, 3259 KiB  
Article
Paraoxonase-1 and -3 Protein Expression in the Brain of the Tg2576 Mouse Model of Alzheimer’s Disease
by Jose Gregorio Salazar, Judit Marsillach, Ingrid Reverte, Bharti Mackness, Michael Mackness, Jorge Joven, Jordi Camps and Maria Teresa Colomina
Antioxidants 2021, 10(3), 339; https://doi.org/10.3390/antiox10030339 - 24 Feb 2021
Cited by 14 | Viewed by 2233
Abstract
Background: Brain oxidative lipid damage and inflammation are common in neurodegenerative diseases such as Alzheimer’s disease (AD). Paraoxonase-1 and -3 (PON1 and PON3) protein expression was demonstrated in tissue with no PON1 or PON3 gene expression. In the present study, we examine differences [...] Read more.
Background: Brain oxidative lipid damage and inflammation are common in neurodegenerative diseases such as Alzheimer’s disease (AD). Paraoxonase-1 and -3 (PON1 and PON3) protein expression was demonstrated in tissue with no PON1 or PON3 gene expression. In the present study, we examine differences in PON1 and PON3 protein expression in the brain of a mouse model of AD. Methods: we used peroxidase- and fluorescence-based immunohistochemistry in five brain regions (olfactory bulb, forebrain, posterior midbrain, hindbrain and cerebellum) of transgenic (Tg2576) mice with the Swedish mutation (KM670/671NL) responsible for a familial form of AD and corresponding wild-type mice. Results: We found intense PON1 and PON3-positive staining in star-shaped cells surrounding Aβ plaques in all the studied Tg2576 mouse-brain regions. Although we could not colocalize PON1 and PON3 with astrocytes (star-shaped cells in the brain), we found some PON3 colocalization with microglia. Conclusions: These results suggest that (1) PON1 and PON3 cross the blood–brain barrier in discoidal high-density lipoproteins (HDLs) and are transferred to specific brain-cell types; and (2) PON1 and PON3 play an important role in preventing oxidative stress and lipid peroxidation in particular brain-cell types (likely to be glial cells) in AD pathology and potentially in other neurodegenerative diseases as well. Full article
(This article belongs to the Special Issue Paraoxonase-1 and Other HDL Accessory Proteins in Neurological Diseases)
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12 pages, 1737 KiB  
Article
Reevaluation of Serum Arylesterase Activity in Neurodevelopmental Disorders
by Ignazio Stefano Piras, Stefano Gabriele, Laura Altieri, Federica Lombardi, Roberto Sacco, Carla Lintas, Barbara Manzi, Paolo Curatolo, Maria Nobile, Catia Rigoletto, Massimo Molteni and Antonio M. Persico
Antioxidants 2021, 10(2), 164; https://doi.org/10.3390/antiox10020164 - 22 Jan 2021
Cited by 5 | Viewed by 2058
Abstract
Organophosphate compounds (OPs) interfere with neurodevelopment and are neurotoxic for humans and animals. They are first biotransformed to the more toxic oxon form, and then hydrolyzed to specific metabolites by the enzyme paraoxonase/arylesterase, encoded by the gene PON1 located on human chr. 7q21.3. [...] Read more.
Organophosphate compounds (OPs) interfere with neurodevelopment and are neurotoxic for humans and animals. They are first biotransformed to the more toxic oxon form, and then hydrolyzed to specific metabolites by the enzyme paraoxonase/arylesterase, encoded by the gene PON1 located on human chr. 7q21.3. In autism spectrum disorder (ASD) and in attention-deficit/hyperactivity disorder (ADHD), a correlation between OP exposure and disease onset has been reported. In this case-control study, we aimed to replicate our previous work showing reduced levels of serum PON1 arylesterase activity in Italian and Caucasian-American ASD samples, and to extend our analysis to other neurodevelopmental disorders, namely ADHD and developmental language disorder (DLD), also known as specific language impairment (SLI). The arylesterase activity, measured using standard spectrophotometric methods, is significantly reduced in the ADHD, and not in the ASD sample compared with the controls. Our previous results seemingly stem from spuriously high arylesterase levels in the former control sample. Finally, genotyping SNPs rs705379 and rs662 using TDI-FP, a significant effect of rs705379 alleles on the serum arylesterase activity is observed in all of the subgroups tested, regardless of diagnosis, as well as a lack of association between PON1 gene polymorphisms and ASD/ADHD susceptibility in the Italian population. In summary, the serum arylesterase activity is reduced in children and adolescents with ADHD, and this reduction is not due to the functional PON1 gene variants assessed in this study. Based on previous literature, it may more likely reflect enhanced oxidative stress than specific genetic underpinnings. Full article
(This article belongs to the Special Issue Paraoxonase-1 and Other HDL Accessory Proteins in Neurological Diseases)
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13 pages, 1634 KiB  
Article
Arylesterase Activity of Paraoxonase-1 in Serum and Cerebrospinal Fluid of Patients with Alzheimer’s Disease and Vascular Dementia
by Arianna Romani, Alessandro Trentini, Wiesje M. van der Flier, Tiziana Bellini, Giovanni Zuliani, Carlo Cervellati and Charlotte E. Teunissen
Antioxidants 2020, 9(5), 456; https://doi.org/10.3390/antiox9050456 - 25 May 2020
Cited by 17 | Viewed by 3156
Abstract
Background: It has been suggested that circulating Paraoxonase-1 (PON1) and apolipoprotein A1 (APOA1), which closely interacts with the antioxidant enzyme, could be implicated in Alzheimer’s disease (AD) and vascular dementia (VaD) development. This study aimed to evaluate PON1 changes in serum and cerebrospinal [...] Read more.
Background: It has been suggested that circulating Paraoxonase-1 (PON1) and apolipoprotein A1 (APOA1), which closely interacts with the antioxidant enzyme, could be implicated in Alzheimer’s disease (AD) and vascular dementia (VaD) development. This study aimed to evaluate PON1 changes in serum and cerebrospinal fluid (CSF) as evidence for its association with AD or VaD. Methods: Serum PON-arylesterase activity was measured in patients with AD, VaD, and CONTROLS distributed in two cohorts: Ferrara cohort (FC: n = 503, age = 74 years) and Amsterdam Dementia cohort (ADC: n = 71, age = 65 years). In the last cohort, CSF PON-arylesterase, CSF β-amyloid1-42, p-tau and t-tau, and imaging biomarkers were also measured. Results: AD and VaD patients of FC showed significantly lower levels of serum PON-arylesterase compared to CONTROLS, but this outcome was driven by older subjects (>71 years, p < 0.0001). In the younger ADC, a similar decreasing (but not significant) trend was observed in serum and CSF. Intriguingly, PON-arylesterase per APOA1 correlated with t-tau in AD group (r = −0.485, p = 0.002). Conclusion: These results suggest that decreased peripheral PON-arylesterase might be a specific feature of older AD/VaD patients. Moreover, we showed that PON-arylesterase/APOA1 is inversely related to neurodegeneration in AD patients, suggesting a prognostic usefulness of this composite parameter. Full article
(This article belongs to the Special Issue Paraoxonase-1 and Other HDL Accessory Proteins in Neurological Diseases)
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Review

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26 pages, 8542 KiB  
Review
Paraoxonase Role in Human Neurodegenerative Diseases
by Cadiele Oliana Reichert, Debora Levy and Sergio P. Bydlowski
Antioxidants 2021, 10(1), 11; https://doi.org/10.3390/antiox10010011 - 24 Dec 2020
Cited by 22 | Viewed by 3820
Abstract
The human body has biological redox systems capable of preventing or mitigating the damage caused by increased oxidative stress throughout life. One of them are the paraoxonase (PON) enzymes. The PONs genetic cluster is made up of three members (PON1, PON2, PON3) that [...] Read more.
The human body has biological redox systems capable of preventing or mitigating the damage caused by increased oxidative stress throughout life. One of them are the paraoxonase (PON) enzymes. The PONs genetic cluster is made up of three members (PON1, PON2, PON3) that share a structural homology, located adjacent to chromosome seven. The most studied enzyme is PON1, which is associated with high density lipoprotein (HDL), having paraoxonase, arylesterase and lactonase activities. Due to these characteristics, the enzyme PON1 has been associated with the development of neurodegenerative diseases. Here we update the knowledge about the association of PON enzymes and their polymorphisms and the development of multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD) and Parkinson’s disease (PD). Full article
(This article belongs to the Special Issue Paraoxonase-1 and Other HDL Accessory Proteins in Neurological Diseases)
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24 pages, 944 KiB  
Review
HDL Proteome and Alzheimer’s Disease: Evidence of a Link
by Judit Marsillach, Maria Pia Adorni, Francesca Zimetti, Bianca Papotti, Giovanni Zuliani and Carlo Cervellati
Antioxidants 2020, 9(12), 1224; https://doi.org/10.3390/antiox9121224 - 03 Dec 2020
Cited by 28 | Viewed by 3755
Abstract
Several lines of epidemiological evidence link increased levels of high-density lipoprotein-cholesterol (HDL-C) with lower risk of Alzheimer’s disease (AD). This observed relationship might reflect the beneficial effects of HDL on the cardiovascular system, likely due to the implication of vascular dysregulation in AD [...] Read more.
Several lines of epidemiological evidence link increased levels of high-density lipoprotein-cholesterol (HDL-C) with lower risk of Alzheimer’s disease (AD). This observed relationship might reflect the beneficial effects of HDL on the cardiovascular system, likely due to the implication of vascular dysregulation in AD development. The atheroprotective properties of this lipoprotein are mostly due to its proteome. In particular, apolipoprotein (Apo) A-I, E, and J and the antioxidant accessory protein paraoxonase 1 (PON1), are the main determinants of the biological function of HDL. Intriguingly, these HDL constituent proteins are also present in the brain, either from in situ expression, or derived from the periphery. Growing preclinical evidence suggests that these HDL proteins may prevent the aberrant changes in the brain that characterize AD pathogenesis. In the present review, we summarize and critically examine the current state of knowledge on the role of these atheroprotective HDL-associated proteins in AD pathogenesis and physiopathology. Full article
(This article belongs to the Special Issue Paraoxonase-1 and Other HDL Accessory Proteins in Neurological Diseases)
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