Peripheral Inflammation Is Associated with Dopaminergic Degeneration in Parkinson's Disease

Muñoz‐Delgado, Laura; Labrador‐Espinosa, Miguel A.; Macías‐García, Daniel; Jesús, Silvia; Zamora, Belén Benítez; Fernández-Rodríguez, Paula; Gómez, A.; Castillo, María Isabel Reina; Castro-Labrador, Sandra; Silva‐Rodríguez, Jesús; Carrillo, Fátima; Solís, David García; Grothe, Michel J.; Mir, Pablo

doi:10.1002/mds.29369

Cited by 10 publications

(4 citation statements)

References 40 publications

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“…Researchers enrolled 344 de novo patients with PD from an international, prospective, longitudinal cohort study named the Parkinson’s Progression Markers Initiative (PPMI) to explore the association about peripheral inflammation and dopaminergic degeneration. The results demonstrated a negative correlation between striatal dopaminergic degeneration and NLR in newly diagnosed PD patients ( Muñoz-Delgado et al, 2023 ).…”

Section: Discussionmentioning

confidence: 92%

Association analysis of dopaminergic degeneration and the neutrophil-to-lymphocyte ratio in Parkinson’s disease

Zhang,

Chen,

Ren

et al. 2024

Front. Aging Neurosci.

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IntroductionPeripheral inflammatory responses are suggested to play a major role in the pathophysiology of Parkinson’s disease (PD). The neutrophil-to-lymphocyte ratio (NLR), a new recognized biomarker, can reflect peripheral inflammation in PD. However, the association between the NLR and dopaminergic degeneration in PD remains unclear.MethodsIn this retrospective study, 101 enrolled PD patients were categorized into early-stage and advanced-stage PD based on the Hoehn and Yahr (HY) scale. We evaluated the clinical characteristics, peripheral immune profile, and 11C-CFT striatal dopamine transporter (DAT) binding levels. Linear regression analyses were employed to assess the associations between NLR and striatal DAT levels at different stages in PD patients.ResultsCovariate-controlled regression analysis revealed that higher NLR was significantly associated with lower DAT levels in the caudate (β = −0.27, p = 0.003) and the putamen (β = −0.27, p = 0.011). Moreover, in the early-stage PD subgroup, a similar association was observed (caudate: β = −0.37, p = 0.013; putamen: β = −0.45, p = 0.005). The lymphocytes count was correlated positively with the striatal DAT levels in the Spearman correlation analysis whether in total patients (caudate: ρ = 0.25, p = 0.013; putamen: ρ = 0.22, p = 0.026) or in the early-stage subgroup (caudate: ρ = 0.31, p = 0.023, putamen: ρ = 0.34, p = 0.011).ConclusionDopaminergic degeneration is associated with peripheral inflammation in PD. The NLR, a widely used inflammatory marker, may have the potential to reflect the degree of dopaminergic degeneration in individuals with early-stage PD.

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Section: Discussionmentioning

confidence: 92%

Association analysis of dopaminergic degeneration and the neutrophil-to-lymphocyte ratio in Parkinson’s disease

Zhang,

Chen,

Ren

et al. 2024

Front. Aging Neurosci.

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“…Additionally, leukocytes and their subpopulations are also reported to be quantitatively and qualitatively altered in peripheral blood ( 23 , 36 , 39 ). Furthermore, inflammatory factors or immune cells abnormally activated in the periphery may infiltrate the central nervous system, thereby potentially triggering inflammation within the central nervous system, which could result in the degeneration of dopaminergic neurons ( 40 , 41 ). In summary, peripheral inflammation is crucial in the pathogenesis of PD.…”

Section: Discussionmentioning

confidence: 99%

The neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and neutrophil-to-high-density-lipoprotein ratio are correlated with the severity of Parkinson’s disease

Li,

Weng,

Zhou

et al. 2024

Front. Neurol.

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BackgroundInflammation plays a pivotal role in the pathogenesis of Parkinson’s disease (PD). However, the correlation between peripheral inflammatory markers and the severity of PD remains unclear.MethodsThe following items in plasma were collected for assessment among patients with PD (n = 303) and healthy controls (HCs; n = 303) were assessed for the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-high-density-lipoprotein ratio (NHR) in plasma, and neuropsychological assessments were performed for all patients with PD. Spearman rank or Pearson correlation was used to evaluate the correlation between the NLR, the LMR and the NHR and the severity of PD. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the NLR, LMR and NHR for PD.ResultsThe plasma NLR and NHR were substantially higher in patients with PD than in HCs, while the plasma LMR was substantially lower. The plasma NLR was positively correlated with Hoehn and Yahr staging scale (H&Y), Unified Parkinson’s Disease Rating Scale (UPDRS), UPDRS-I, UPDRS-II, and UPDRS-III scores. Conversely, it exhibited a negative relationship with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Furthermore, the plasma NHR was positively correlated with H&Y, UPDRS, UPDRS-I, UPDRS-II and UPDRS-III scores. Moreover, negative associations were established between the plasma LMR and H&Y, UPDRS, UPDRS-I, UPDRS-II, and UPDRS-III scores. Finally, based on the ROC curve analysis, the NLR, LMR and NHR exhibited respectable PD discriminating power.ConclusionOur research indicates that a higher NLR and NHR and a lower LMR may be relevant for assessing the severity of PD and appear to be promising disease-state biomarker candidates.

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“…These intracellular signals include transcriptional and translational inhibition which decrease the ER concentration of proteins and boost the number of molecular chaperones to improve the ER capacity for folding [272]. The peripheral inflammation in PD is exacerbated by lymph node swelling, which is directly associated with macrophage activation and is brought on by meningeal lymphatics discharging oligomeric α-syn [273,274]. ER stress caused by oligomeric α-syn is amongst the most plausible causes of PD.…”

Section: Er Stressmentioning

confidence: 99%

Advancements in Genetic and Biochemical Insights: Unraveling the Etiopathogenesis of Neurodegeneration in Parkinson’s Disease

Ratan,

Rajput,

Pareek

et al. 2024

Biomolecules

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Parkinson’s disease (PD) is the second most prevalent neurodegenerative movement disorder worldwide, which is primarily characterized by motor impairments. Even though multiple hypotheses have been proposed over the decades that explain the pathogenesis of PD, presently, there are no cures or promising preventive therapies for PD. This could be attributed to the intricate pathophysiology of PD and the poorly understood molecular mechanism. To address these challenges comprehensively, a thorough disease model is imperative for a nuanced understanding of PD’s underlying pathogenic mechanisms. This review offers a detailed analysis of the current state of knowledge regarding the molecular mechanisms underlying the pathogenesis of PD, with a particular emphasis on the roles played by gene-based factors in the disease’s development and progression. This study includes an extensive discussion of the proteins and mutations of primary genes that are linked to PD, including α-synuclein, GBA1, LRRK2, VPS35, PINK1, DJ-1, and Parkin. Further, this review explores plausible mechanisms for DAergic neural loss, non-motor and non-dopaminergic pathologies, and the risk factors associated with PD. The present study will encourage the related research fields to understand better and analyze the current status of the biochemical mechanisms of PD, which might contribute to the design and development of efficacious and safe treatment strategies for PD in future endeavors.

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Peripheral Inflammation Is Associated with Dopaminergic Degeneration in Parkinson's Disease

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 10 publications

References 40 publications

Association analysis of dopaminergic degeneration and the neutrophil-to-lymphocyte ratio in Parkinson’s disease

Association analysis of dopaminergic degeneration and the neutrophil-to-lymphocyte ratio in Parkinson’s disease

The neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and neutrophil-to-high-density-lipoprotein ratio are correlated with the severity of Parkinson’s disease

Advancements in Genetic and Biochemical Insights: Unraveling the Etiopathogenesis of Neurodegeneration in Parkinson’s Disease

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