Lower levels of uric acid and striatal dopamine in non-tremor dominant Parkinson's disease subtype

Huertas, Ismael; Jesús, Silvia; Lojo, J. A.; García-Gómez, Francisco Javier; Cáceres‐Redondo, María T.; Oropesa-Ruiz, Juan Manuel; Carrillo, Fátima; Vargas‐González, Laura; Rodríguez, Jesús Núñez; Gómez-Garre, Pilar; García-Solís, David; Mir, Pablo

doi:10.1371/journal.pone.0174644

Cited by 26 publications

(24 citation statements)

References 30 publications

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“…IBIL (μmol/L) was divided into four groups (group 1: < 1.7; group 2: ≥1.7 and < 6.8; group 3: ≥6.8 and < 13.7; group 4: ≥13.7) with the 25, 100, and 200% of the official reference limit (< 6.8) as the dividing point. LEDD (mg/day) was divided into four groups (0-300, 300-600, 600-900, 900-1,200) with the 25, 50, and 75% of the maximum LEDD of the patients in this study (1,200 Descriptive values and statistics are shown in Table 1. Compared to controls, significantly lower TBIL and IBIL concentrations and significantly higher DBIL concentration were observed in PD subjects (TBIL, p = 0.003; IBIL, p < 0.001; DBIL, p < 0.001) ( Table 1).…”

Section: Discussionmentioning

confidence: 99%

“…Parkinson's disease (PD) has high clinical heterogeneity. Based on the motor symptoms, PD patients can be classified into tremor-dominant (TD), intermediate (I), and postural instability and gait disorder (PIGD) subtypes [1]. It is found that different motor subtypes have different prognoses.…”

Section: Introductionmentioning

confidence: 99%

“…DOI: 10.1159/000505852 A major challenge is to unravel why different Parkinson's patients present with different subtypes of motor symptoms. It is likely that multiple factors play roles in the pathogenesis of PD phenotype, including mitochondrial function defects, abnormal protein regulation, and consecutive oxidative stress [1,3]. Bilirubin is an important natural antioxidant in the human body and is a major contributor to the total antioxidant capacity of plasma [4].…”

Section: Introductionmentioning

confidence: 99%

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Association of Serum Indirect Bilirubin Concentrations with Motor Subtypes of Parkinson’s Disease

Zhao

Zhong

et al. 2019

Neurodegener Dis

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Introduction: We aimed to investigate the change of serum indirect bilirubin (IBIL) concentrations in patients with Parkinson's disease (PD) and whether IBIL concentrations were associated with the motor subtypes of PD. Methods: A casecontrol study was performed to evaluate differences in bilirubin concentrations between 78 PD subjects and 78 controls. Venous blood samples were collected, and total bilirubin (TBIL), direct bilirubin (DBIL), and IBIL concentrations were analyzed between PD subjects and controls. PD patients were classified into three motor subtypes: tremordominant (TD), intermediate (I), and postural instability and gait disorder (PIGD). It was evaluated whether there were differences in IBIL concentrations between the different motor subtypes and between motor subtypes and controls. Results: PD patients had lower IBIL concentrations compared to controls (6.51 ± 4.03 vs. 10.82 ± 4.61, p < 0.001). There was no significant difference in IBIL concentrations between PD males and PD females (6.66 ± 3.64 vs. 6.22 ± 4.79, p = 0.655).IBIL concentrations had negative relationships with levodopa-equivalent daily dose (LEDD) (R = -0.452, p < 0.001) and positive relationships with tremor score (R = 0.360, p = 0.001). IBIL concentrations were significantly lower for PIGD than for TD subtype (4.88 ± 4.03 vs. 9.00 ± 4.15, p < 0.001). The lower IBIL concentrations in PD compared to controls were mainly driven by the PIGD patients. Conclusions: PD subjects showed lower levels of IBIL compared to controls. Higher IBIL levels were associated with TD motor subtype in PD, which could be related to the antioxidative properties of IBIL.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of Serum Indirect Bilirubin Concentrations with Motor Subtypes of Parkinson’s Disease

Zhao

Zhong

et al. 2019

Neurodegener Dis

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“…Importantly, patients with tremor dominant PD had a disease duration of 9.4 years ( SEM 1.5) compared with 5.8 years ( SEM 0.6) for patients with the akinetic‐rigid phenotype and these differences may have contributed to the findings but despite the heterogeneity of PD, there have been multiple studies suggesting patients with a tremor dominant phenotype have a less aggressive disease course, with less pathological burden and a lower degree of dopaminergic denervation(Eggers et al., ; Huertas et al., ; Selikhova et al., ). This fact, taken together with our observation that patients with lower disability as rated by lower MDS‐UPDRS Part 2 scores, may indicate that patients with less aggressive, milder disease load may have more compensatory mechanisms for exenatide to exert any disease‐modifying effects.…”

Section: Discussionmentioning

confidence: 99%

Post hoc analysis of the Exenatide‐PD trial—Factors that predict response

Athauda

Maclagan

Budnik³

et al. 2018

Eur J of Neuroscience

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Exenatide, a glucagon-like peptide-1 agonist and a licensed treatment for Type 2 diabetes significantly reduced deterioration in motor symptoms in patients with Parkinson's disease in a randomized, placebo-controlled trial. In addition, there were trends favouring the exenatide group in assessments of nonmotor symptoms, cognition, and quality of life. The aim of this exploratory post hoc analysis was to generate new hypotheses regarding (a) whether candidate baseline factors might predict the magnitude of response to exenatide; and (b) whether the beneficial effects of exenatide reported for the overall population are consistent in various subgroups of patients. Univariate and multivariate analyses were conducted to determine possible predictors of motor response to exenatide in this cohort. Potential treatment by subgroup interactions for changes in; motor severity, nonmotor symptoms, cognition, and quality of life after 48-weeks treatment with exenatide were evaluated among post hoc subgroups defined by age, motor phenotype, disease duration, disease severity, body mass index (BMI), and insulin resistance. In the subgroup analyses, exenatide once-weekly was associated with broadly improved outcome measures assessing motor severity, nonmotor symptoms, cognition, and quality of life across all subgroups, however, tremor-dominant phenotype and lower Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part-2 scores predicted greatest motor response to exenatide and there was an indication that patients with older age of onset and disease duration over 10 years responded less well. While patients with a range of demographic and clinical factors can potentially benefit from exenatide once-weekly, these data support an emphasis towards recruiting patients at earlier disease in future planned clinical trials of gluacagon-like peptide-1 (GLP-1) receptor agonists in Parkinson's disease (PD).

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“…Supõe-se ser a forma tremulante da DP de melhor prognóstico quando comparada as formas rígidoacinéticas. Maiores níveis de AU são observados em pacientes com a forma tremulante da DP em comparação as formas rígido-acinéticas34 . Ressalte-se que a terapia com levodopa sabidamente aumenta a reabsorção renal de acido úrico.…”

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Participação do ácido úrico em doenças neurodegenerativas

Vilaça¹,

Ribas²,

Leite³

et al. 2019

Rev Neurocienc

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Objetivo. Revisão abordando a correlação entre os níveis de ácido úrico e doenças neurodegenerativas. Método. Revisão não sistemática utilizando a plataforma Google Acadêmico de artigos relacionando os níveis de ácido úrico em doenças neurodegenerativas de alta prevalência. Resultados. Foram utilizados 70 artigos em inglês para confecção desta revisão. Conclusão. O ácido úrico principalmente através de seu efeito antioxidante pode participar da fisiopatologia de diversas condições neurodegenerativas. Sendo um biomarcador de mensuração fácil e de baixo custo estudos sobre o ácido úrico poderão auxiliar no diagnóstico, prognóstico e terapias destas patologias neurodegenerativas.

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Lower levels of uric acid and striatal dopamine in non-tremor dominant Parkinson's disease subtype

Cited by 26 publications

References 30 publications

Association of Serum Indirect Bilirubin Concentrations with Motor Subtypes of Parkinson’s Disease

Association of Serum Indirect Bilirubin Concentrations with Motor Subtypes of Parkinson’s Disease

Post hoc analysis of the Exenatide‐PD trial—Factors that predict response

Participação do ácido úrico em doenças neurodegenerativas

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