Decreased arylesterase activity of paraoxonase-1 (PON-1) might be a common denominator of neuroinflammatory and neurodegenerative diseases.
High-density lipoprotein (HDL)-bound paraoxonase-1 (PON-1) is mechanistically related to oxidative stress, inflammation and atherosclerosis and this multirole nature positions the enzyme as potential pathogenic player and candidate biomarker for many diseases. Our previous work suggests that decline in serum PON-1 activities, i.e. arylesterase and paraoxonase, might be associated with the occurrence of mild cognitive impairment (MCI) to late onset Alzheimer's disease (LOAD) or vascular dementia (VAD). The present study aimed to: (1) expand our previous findings in a larger and different population, including patients with LOAD-VAD mixed dementia (MD); (2) explore a possible association between PON-1 and multiple sclerosis (MS); (3) evaluate if cerebrospinal fluid (CSF) levels of PON-1 activities might be useful biomarkers for MS. We found that serum arylesterase, but not paraoxonase, levels of PON-1 were significantly lower in patients affected by MCI (n=232), VAD (n=65), LOAD (n=175), MD (n=88) as well as those with MS (n=104) as compared to healthy controls. Notably, the most pronounced decline in this activity was shown by MD (-18%, p<0.01) and MS (-23%, p<0.001), while the lowest changes were detected in the MCI group (11%, p<0.05). Only arylesterase was detectable in the CSF of MS patients and the levels were not significantly different from those detected in the other two neurological control groups. Overall our data suggest that a depressed arylesterase activity could be a common denominator of different neurological diseases which, independently of their peculiar ethiopathogenesis and pathophysiology, appear to be all characterized by an altered systemic redox balance.
Department of Biomedical and Specialist Surgical Sciences, Section of Neurological, Psychiatric and Psychological Sciences University of Ferrara, 44124 Ferrara, Italy.
Massimiliano
M
Castellazzi
Department of Biomedical and Specialist Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics University of Ferrara, 44121, Ferrara, Italy.
Alessandro
A
Trentini
Department of Biomedical and Specialist Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics University of Ferrara, 44121, Ferrara, Italy.
Arianna
A
Romani
Department of Life Sciences and Biotechnology, University of Ferrara, Via Borsari 46, 44121, Ferrara, Italy.
Giuseppe
G
Valacchi
Department of Biomedical and Specialist Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics University of Ferrara, 44121, Ferrara, Italy.
Tiziana
T
Bellini
Department of Morphology, Surgery and Experimental Medicine, Menopause and Osteoporosis Centre, University of Ferrara, Ferrara, Italy.
Gloria
G
Bonaccorsi
Department of Diagnostic Imaging, Neuroradiology Unit, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
Enrico
E
Fainardi
Department of Life Sciences and Biotechnology, University of Ferrara, Via Borsari 46, 44121, Ferrara, Italy.
Carlotta
C
Cavicchio
Department of Medical Science, Section of Internal Medicine, Gerontology, and Clinical Nutrition, University of Ferrara, 44100, Ferrara, Italy.
Angelina
A
Passaro
Department of Medical Science, Section of Internal Medicine, Gerontology, and Clinical Nutrition, University of Ferrara, 44100, Ferrara, Italy.
Giovanni
G
Zuliani
Department of Biomedical and Specialist Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics University of Ferrara, 44121, Ferrara, Italy. Electronic address: crvcrl@unife.it.
Carlo
C
Cervellati
D000368:Aged; D043303:Aryldialkylphosphatase / Q000097:blood* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases / Q000097:blood* / Q000378:metabolism; D003704:Dementia / Q000097:blood / Q000175:diagnosis / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood / Q000175:diagnosis* / Q000201:enzymology* / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000097:blood / Q000175:diagnosis* / Q000201:enzymology* / Q000378:metabolism; D012307:Risk Factors
D015415:Biomarkers; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase; D043303:Aryldialkylphosphatase
Alzheimer’s disease; Arylesterase activity; Multiple sclerosis; Paraoxonase-1; Vascular dementia