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Investigation of paraoxonase-1 genotype and enzyme-kinetic parameters in the context of cognitive impairment in Parkinson’s disease
ID
Petrič, Boštjan
(
Avtor
),
ID
Redenšek Trampuž, Sara
(
Avtor
),
ID
Dolžan, Vita
(
Avtor
),
ID
Gregorič Kramberger, Milica
(
Avtor
),
ID
Trošt, Maja
(
Avtor
),
ID
Maraković, Nikola
(
Avtor
),
ID
Goličnik, Marko
(
Avtor
),
ID
Bavec, Aljoša
(
Avtor
)
PDF - Predstavitvena datoteka,
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MD5: 45C1E6CCE7C962A97D878B5063419FCC
URL - Izvorni URL, za dostop obiščite
https://www.mdpi.com/2076-3921/12/2/399
Galerija slik
Izvleček
Cognitive impairment is a common non-motor symptom of Parkinson’s disease (PD), which often progresses to PD dementia. PD patients with and without dementia may differ in certain biochemical parameters, which could thus be used as biomarkers for PD dementia. The enzyme paraoxonase 1 (PON1) has previously been investigated as a potential biomarker in the context of other types of dementia. In a cohort of PD patients, we compared a group of 89 patients with cognitive impairment with a group of 118 patients with normal cognition. We determined the kinetic parameters K$_m$ and V$_{max}$ for PON1 for the reaction with dihydrocoumarin and the genotype of four single nucleotide polymorphisms in PON1. We found that no genotype or kinetic parameter correlated significantly with cognitive impairment in PD patients. However, we observed associations between PON1 rs662 and PON1 K$_m$ (p < 10$^{−10}$), between PON1 rs662 and PON1 V$_{max}$ (p = 9.33 × 10$^{−7}$), and between PON1 rs705379 and PON1 V$_{max}$ (p = 2.21 × 10$^{−10}$). The present study is novel in three main aspects. (1) It is the first study to investigate associations between the PON1 genotype and enzyme kinetics in a large number of subjects. (2) It is the first study to report kinetic parameters of PON1 in a large number of subjects and to use time-concentration progress curves instead of initial velocities to determine K$_m$ and V$_{max}$ in a clinical context. (3) It is also the first study to calculate enzyme-kinetic parameters in a clinical context with a new algorithm for data point removal from progress curves, dubbed iFIT. Although our results suggest that in the context of PD, there is no clinically useful correlation between cognitive status on the one hand and PON1 genetic and enzyme-kinetic parameters on the other hand, this should not discourage future investigation into PON1’s potential associations with other types of dementia.
Jezik:
Angleški jezik
Ključne besede:
Parkinson disease
,
cognitive impairment
,
paraoxonase 1
,
paraoxonase activity
,
single-nucleotide polymorphisms
,
iFIT
Vrsta gradiva:
Članek v reviji
Tipologija:
1.01 - Izvirni znanstveni članek
Organizacija:
MF - Medicinska fakulteta
Status publikacije:
Objavljeno
Različica publikacije:
Objavljena publikacija
Leto izida:
2023
Št. strani:
16 str.
Številčenje:
Vol. 12, iss. 2, art. 399
PID:
20.500.12556/RUL-154047
UDK:
616.8
ISSN pri članku:
2076-3921
DOI:
10.3390/antiox12020399
COBISS.SI-ID:
141510403
Datum objave v RUL:
22.01.2024
Število ogledov:
337
Število prenosov:
27
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Objavi na:
Gradivo je del revije
Naslov:
Antioxidants
Skrajšan naslov:
Antioxidants
Založnik:
MDPI
ISSN:
2076-3921
COBISS.SI-ID:
522976025
Licence
Licenca:
CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:
http://creativecommons.org/licenses/by/4.0/deed.sl
Opis:
To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
Sekundarni jezik
Jezik:
Slovenski jezik
Ključne besede:
Parkinsonova bolezen
,
kognitivne motnje
,
paraoksonaza 1
Projekti
Financer:
ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:
P1-0170
Naslov:
Molekulski mehanizmi uravnavanja celičnih procesov v povezavi z nekaterimi boleznimi pri človeku
Financer:
ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:
J7-2600
Naslov:
Presnovne možganske spremembe nevrodegenerativnih demenc in njihove korelacije s histopatološkimi spremembami v možganih
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