PON-1 and ferroxidase activities in older patients with mild cognitive impairment, late onset Alzheimer’s disease or vascular dementia

Cervellati, Carlo; Romani, Arianna; Bergamini, Carlo M.; Bosi, Cristina; Sanz, Juana María; Passaro, Angelina; Zuliani, Giovanni

doi:10.1515/cclm-2014-0803

Cited by 31 publications

(48 citation statements)

References 50 publications

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“…Furthermore, PON-1 might not have a high clinical specificity for AD, being a multifactorial enzyme widely associated with many different disorders 150 152 153…”

Section: Involvement Of Oxs In Ad Pathogenesismentioning

confidence: 99%

Oxidative Challenge in Alzheimer's Disease: State of Knowledge and Future Needs

Cervellati

Wood

Romani

et al. 2016

Journal of Investigative Medicine

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A large body of experimental and postmortem findings indicate that Alzheimer's disease (AD) is associated with increased oxidative stress (OxS) levels in the brain. Despite the current limitations of OxS assessment in living subjects, recent data suggest that oxidative challenge might increase early both in the central nervous system and peripheral fluids. The aim of this review was to provide an overview of the existing literature linking systemic OxS to brain OxS in AD. We firmly believe that continued research aimed at overcoming the methodological and design issues affecting the body of studies in this field is mandatory for successful development of an effective antioxidant-based treatment of AD.

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“…Furthermore, PON-1 might not have a high clinical specificity for AD, being a multifactorial enzyme widely associated with many different disorders 150 152 153…”

Section: Involvement Of Oxs In Ad Pathogenesismentioning

confidence: 99%

Oxidative Challenge in Alzheimer's Disease: State of Knowledge and Future Needs

Cervellati

Wood

Romani

et al. 2016

Journal of Investigative Medicine

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“…Even if the time-course of the pathogenic progression is unclear, aggregation of amyloid β (Aβ) to form extracellular senile plaques, neurofibrillary tangles and mitochondrial dysfunction play primary roles in AD development and clinical progression [98]. Cerebrovascular lesions and defects in brain micro-circulation are frequent pathological traits of this disease [99] and are, to various extents, related to OxS [13,15,98,100,101].…”

Section: Alzheimer's Diseasementioning

confidence: 99%

Oxidative damage and the pathogenesis of menopause related disturbances and diseases

Cervellati

Bergamini

2016

Clinical Chemistry and Laboratory Medicine (CCLM)

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Abstract:The postmenopausal phase of life is frequently associated in women with subjective symptoms (e.g. vasomotor) and real diseases (atherosclerosis with coronary ischemia, osteoporosis, Alzheimer-type neurodegeneration, urogenital dystrophy), which together determine the post-menopausal syndrome. Observations that oxidative damage by reactive oxygen/nitrogen species in experimental models can contribute to the pathogenesis of these disturbances stimulated research on the relationships between menopause, its endocrine deficiency, oxidative balance and the "wellness" in postmenopausal life. The connection among these events is probably due to the loss of protective actions exerted by estrogens during the fertile life. Most recent studies have revealed that estrogens exert an antioxidant action not by direct chemical neutralization of reactants as it was expected until recently but by modulating the expression of antioxidant enzymes that control levels of biological reducing agents. Also nutritional antioxidants apparently act by a similar mechanism. From this perspective it is conceivable that a cumulative control of body oxidant challenges and biological defenses could help in monitoring between "normal" and "pathological" menopause. However, as clinical studies failed to confirm this scenario in vivo, we have decided to review the existing literature to understand the causes of this discrepancy and whether this was due to methodologic reasons or to real failure of the basic hypothesis.

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“…We have previously reported statistical interactions between this variant and OP exposures related to PD risk (Lee et al 2013), and there is evidence for a role of PON1 in Alzheimer's and vascular dementia, potentially through its anti-atherosclerotic function (Wehr et al 2009; Zhub et al 2015). PON1 is an arylesterase, responsible for metabolism of aromatic esters (Cervellati et al 2014). Both paraoxonase and arylesterase activities of the protein are responsible for the anti-inflammatory and antioxidant activities of high density lipoprotein (HDL) and PON1 has been shown to prevent LDL oxidation in-vitro (Cervellati et al 2014).…”

Section: Introductionmentioning

confidence: 99%

“…PON1 is an arylesterase, responsible for metabolism of aromatic esters (Cervellati et al 2014). Both paraoxonase and arylesterase activities of the protein are responsible for the anti-inflammatory and antioxidant activities of high density lipoprotein (HDL) and PON1 has been shown to prevent LDL oxidation in-vitro (Cervellati et al 2014). …”

Section: Introductionmentioning

confidence: 99%

Organophosphate pesticides and PON1 L55M in Parkinson's disease progression

Paul

Sinsheimer

Cockburn

et al. 2017

Environment International

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Background Parkinson's disease (PD) has motor and non-motor features that contribute to its phenotype and functional decline. Organophosphate (OP) pesticides and PON1 L55M, which influences OP metabolism, have been implicated in multiple mechanisms related to neuronal cell death and may influence PD symptom progression. Objective To investigate whether ambient agricultural OP exposure and PON1 L55M influence the rate of motor, cognitive, and mood-related symptom progression in PD. Methods We followed a longitudinal cohort of 246 incident PD patients on average over 5 years (7.5 years after diagnosis), repeatedly measuring symptom progression with the Mini-Mental State Exam (MMSE), Unified Parkinson's Disease Rating Scale (UPDRS), and Geriatric Depressive Scale (GDS). OP exposures were generated with a geographic information system (GIS) based exposure assessment tool. We employed repeated-measures regression to assess associations between OP exposure and/or PON1 L55M genotype and progression. Results High OP exposures were associated with faster progression of motor (UPDRS β=0.24, 95% CI=−0.01, 0.49) and cognitive scores (MMSE β=−0.06, 95% CI=−0.11, −0.01). PON1 55MM was associated with faster progression of motor (UPDRS β=0.28, 95% CI=0.08, 0.48) and depressive symptoms (GDS β=0.07; 95% CI=0.01, 0.13). We also found the PON1 L55M variant to interact with OP exposures in influencing MMSE cognitive scores (β=−1.26, 95% CI=−2.43, −0.09). Conclusion Our study provides preliminary support for the involvement of OP pesticides and PON1 in PD-related motor, cognitive, or depressive symptom progression. Future studies are needed to replicate findings and examine whether elderly populations generally are similarly impacted by pesticides or PON1 55M genotypes.

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PON-1 and ferroxidase activities in older patients with mild cognitive impairment, late onset Alzheimer’s disease or vascular dementia

Abstract: Overall, our results suggest that depression of PON-1, and in particular, of arylesterase activity, in serum might be an early feature of dementia-related diseases. Further longitudinal exploration of the role of this enzyme in the onset and progression of these disorders are required.

Cited by 31 publications

References 50 publications

Oxidative Challenge in Alzheimer's Disease: State of Knowledge and Future Needs

Oxidative Challenge in Alzheimer's Disease: State of Knowledge and Future Needs

Oxidative damage and the pathogenesis of menopause related disturbances and diseases

Organophosphate pesticides and PON1 L55M in Parkinson's disease progression

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