New therapeutic approaches to target alpha-synuclein in Parkinson's disease: The role of immunotherapy

Fernández-Valle, Tamara; Gabilondo, Iñigo; Gómez‐Esteban, Juan Carlos

doi:10.1016/bs.irn.2019.06.014

Cited by 15 publications

(15 citation statements)

References 42 publications

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“…In postmortem brain tissues from patients with α-synucleinopathy, α-Syn accumulation is associated with mitochondrial respiration defects, suggesting that mitochondrial dysfunction is a downstream effect of aggregated α-Syn. Based on this information, Fernández-Valle et al [ 48 ] suggested that targeting the extracellular phase of α-Syn transmission is the most promising immunotherapy approach for Parkinson’s disease due its contribution to neuroinflammation.…”

Section: Discussionmentioning

confidence: 99%

Alpha-Synuclein, cyclooxygenase-2 and prostaglandins-EP2 receptors as neuroinflammatory biomarkers of autism spectrum disorders: Use of combined ROC curves to increase their diagnostic values

et al. 2021

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Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and restricted and repetitive behaviors. Neuroinflammation and abnormal lipid mediators have been identified in multiple investigations as an acknowledged etiological mechanism of ASD that can be targeted for therapeutic intervention. Methods In this study, multiple regression and combined receiver operating characteristic (ROC) curve analyses were used to determine the relationship between the neuroinflammatory marker α-synuclein and lipid mediator markers related to inflammation induction, such as cyclooxygenase-2 and prostaglandin-EP2 receptors, in the etiology of ASD. Additionally, the study aimed to determine the linear combination that maximizes the partial area under ROC curves for a set of markers. Forty children with ASD and 40 age- and sex-matched controls were enrolled in the study. Using ELISA, the levels of α-synuclein, cyclo-oxygenase-2, and prostaglandin-EP2 receptors were measured in the plasma of both groups. Statistical analyses using ROC curves and multiple and logistic regression models were performed. Results A remarkable increase in the area under the curve was observed using combined ROC curve analyses. Moreover, higher specificity and sensitivity of the combined markers were reported. Conclusions The present study indicates that measurement of the predictive value of selected biomarkers related to neuroinflammation and lipid metabolism in children with ASD using a ROC curve analysis should lead to a better understanding of the etiological mechanism of ASD and its link with metabolism. This information may facilitate early diagnosis and intervention.

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Section: Discussionmentioning

confidence: 99%

Alpha-Synuclein, cyclooxygenase-2 and prostaglandins-EP2 receptors as neuroinflammatory biomarkers of autism spectrum disorders: Use of combined ROC curves to increase their diagnostic values

et al. 2021

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“…First immunizations with PD01 induced an immune response against the peptide and against the targeted α-syn epitope, with generation of α-syn antibodies. The boost immunization then showed an increase in reactivity in the immune response [206][207][208].…”

Section: Active Immunizationmentioning

confidence: 99%

Targeting α-Synuclein for PD Therapeutics: A Pursuit on All Fronts

et al. 2020

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Parkinson’s Disease (PD) is characterized both by the loss of dopaminergic neurons in the substantia nigra and the presence of cytoplasmic inclusions called Lewy Bodies. These Lewy Bodies contain the aggregated α-synuclein (α-syn) protein, which has been shown to be able to propagate from cell to cell and throughout different regions in the brain. Due to its central role in the pathology and the lack of a curative treatment for PD, an increasing number of studies have aimed at targeting this protein for therapeutics. Here, we reviewed and discussed the many different approaches that have been studied to inhibit α-syn accumulation via direct and indirect targeting. These analyses have led to the generation of multiple clinical trials that are either completed or currently active. These clinical trials and the current preclinical studies must still face obstacles ahead, but give hope of finding a therapy for PD with time.

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“…The retrospective analysis of patients treated with amantadine showed an improved survival rate (Uitti et al 1996). Memantine exerted a dose-dependent, sustained effect on cortical and hippocampal neurons induced by excitotoxicity and hypoperfusion (Seif el Nasr et al 1990;Erdö and Schäfer 1991). NMDA-receptor antagonists are badly tolerated by patients because of their side effects (e.g., psychiatric symptoms) (Olanow and Jankovic 2005).…”

Section: Nmda Receptor Antagonistsmentioning

confidence: 99%

Neuroprotection in Parkinson’s disease: facts and hopes

et al. 2019

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Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Behind the symptoms there is a complex pathological mechanism which leads to a dopaminergic cell loss in the substantia nigra pars compacta. Despite the strong efforts, curative treatment has not been found yet. To prevent a further cell death, numerous molecules were tested in terms of neuroprotection in preclinical (in vitro, in vivo) and in clinical studies as well. The aim of this review article is to summarize our knowledge about the extensively tested neuroprotective agents (Search period: 1991-2019). We detail the underlying pathological mechanism and summarize the most important results of the completed animal and clinical trials. Although many positive results have been reported in the literature, there is still no evidence that any of them should be used in clinical practice (Cochrane analysis was performed). Therefore, further studies are needed to better understand the pathomechanism of PD and to find the optimal neuroprotective agent(s).

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New therapeutic approaches to target alpha-synuclein in Parkinson's disease: The role of immunotherapy

Cited by 15 publications

References 42 publications

Alpha-Synuclein, cyclooxygenase-2 and prostaglandins-EP2 receptors as neuroinflammatory biomarkers of autism spectrum disorders: Use of combined ROC curves to increase their diagnostic values

Alpha-Synuclein, cyclooxygenase-2 and prostaglandins-EP2 receptors as neuroinflammatory biomarkers of autism spectrum disorders: Use of combined ROC curves to increase their diagnostic values

Targeting α-Synuclein for PD Therapeutics: A Pursuit on All Fronts

Neuroprotection in Parkinson’s disease: facts and hopes

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