Salivary alpha-synuclein (total and oligomeric form): potential biomarkers in Parkinson’s disease

Shaheen, Hala A.; Sobhy, Sayed; Mously, Sherine El; Abuomira, Marwa; Mansour, Mohamed H.

doi:10.1186/s41983-020-0159-7

Cited by 20 publications

(37 citation statements)

References 35 publications

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“…The authors suggested that the decrease in total α-synuclein in saliva in PD subjects could partly be accounted for by the oligomerization of monomeric α-synuclein. Similar findings were reported by Shaheen et al (2020) , which also showed a positive correlation between the level of o-α-syn and disease duration; further, in PD patients, higher levels of o-α-syn were seen in bradykinesia and rigidity-dominant than in tremor-dominant phenotypes. Another study measured the salivary total α-synuclein and o-α-syn between controls and PD cases and analyzed single nucleotide polymorphisms or SNP variants of SNCA in the PD group ( Kang et al, 2016 ).…”

Section: α-Synuclein As a Biomarkersupporting

confidence: 88%

Alpha-Synuclein as a Biomarker of Parkinson’s Disease: Good, but Not Good Enough

Ganguly

Singh

Pal

et al. 2021

Front. Aging Neurosci.

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Parkinson’s disease (PD) is the second most common neurodegenerative disorder of the elderly, presenting primarily with symptoms of motor impairment. The disease is diagnosed most commonly by clinical examination with a great degree of accuracy in specialized centers. However, in some cases, non-classical presentations occur when it may be difficult to distinguish the disease from other types of degenerative or non-degenerative movement disorders with overlapping symptoms. The diagnostic difficulty may also arise in patients at the early stage of PD. Thus, a biomarker could help clinicians circumvent such problems and help them monitor the improvement in disease pathology during anti-parkinsonian drug trials. This review first provides a brief overview of PD, emphasizing, in the process, the important role of α-synuclein in the pathogenesis of the disease. Various attempts made by the researchers to develop imaging, genetic, and various biochemical biomarkers for PD are then briefly reviewed to point out the absence of a definitive biomarker for this disorder. In view of the overwhelming importance of α-synuclein in the pathogenesis, a detailed analysis is then made of various studies to establish the biomarker potential of this protein in PD; these studies measured total α-synuclein, oligomeric, and post-translationally modified forms of α-synuclein in cerebrospinal fluid, blood (plasma, serum, erythrocytes, and circulating neuron-specific extracellular vesicles) and saliva in combination with certain other proteins. Multiple studies also examined the accumulation of α-synuclein in various forms in PD in the neural elements in the gut, submandibular glands, skin, and the retina. The measurements of the levels of certain forms of α-synuclein in some of these body fluids or their components or peripheral tissues hold a significant promise in establishing α-synuclein as a definitive biomarker for PD. However, many methodological issues related to detection and quantification of α-synuclein have to be resolved, and larger cross-sectional and follow-up studies with controls and patients of PD, parkinsonian disorders, and non-parkinsonian movement disorders are to be undertaken.

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Section: α-Synuclein As a Biomarkersupporting

confidence: 88%

Alpha-Synuclein as a Biomarker of Parkinson’s Disease: Good, but Not Good Enough

Ganguly

Singh

Pal

et al. 2021

Front. Aging Neurosci.

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“…In conclusion, this study confirmed the hypothesis of evaluating the total α-synuclein/oligomeric α-synuclein ratio as a possible biomarker in the diagnosis of PD. However, this ratio did not correlate with the severity of PD [41].…”

Section: Salivary Biomarkers In Parkinson's Diseasementioning

confidence: 70%

Salivary Biomarkers: Future Approaches for Early Diagnosis of Neurodegenerative Diseases

et al. 2020

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Many neurological diseases are characterized by progressive neuronal degeneration. Early diagnosis and new markers are necessary for prompt therapeutic intervention. Several studies have aimed to identify biomarkers in different biological liquids. Furthermore, it is being considered whether saliva could be a potential biological sample for the investigation of neurodegenerative diseases. This work aims to provide an overview of the literature concerning biomarkers identified in saliva for the diagnosis of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Specifically, the studies have revealed that is possible to quantify beta-amyloid1–42 and TAU protein from the saliva of AD patients. Instead, alpha-synuclein and protein deglycase (DJ-1) have been identified as new potential salivary biomarkers for the diagnosis of PD. Nevertheless, future studies will be needed to validate these salivary biomarkers in the diagnosis of neurological diseases.

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“…Potential circulating biomarkers for diagnosis, prognosis, and monitoring have been identified in salivary secretions for various diseases, including PD, AD, Sjögren’s syndrome, and oral cancer. 10 – 14 , 31 , 43 , 52 – 54 Among neurodegenerative diseases, like PD, the critical role of oxidative stress in disease pathogenesis have led to increasing research in the use of oxidatively modified nucleic acids, lipids, proteins, and antioxidants such as HO-1, advanced glycation end products, and reduced glutathione as salivary redox biomarkers for diagnostic or prognostic markers of disease. 54 – 58 Saliva has several advantages in comparison to other biofluids for biomarker research such as its non-invasive method of fluid acquisition, the non-extensive requirement for personnel training for saliva specimen collection, and salivary composition being reflective of blood or CSF composition.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9] Several chemical analytes in saliva have been investigated as potential biomarkers for PD, including α-synuclein, protein deglycase DJ-1, and heme oxygenase-1 (HO-1), an inducible enzyme that degrades heme to biliverdin, ferrous iron, and carbon monoxide. [10][11][12][13][14][15][16] The HMOX1 gene contains a panoply of regulatory elements that allows it to respond to numerous stressors such as heme, dopamine, nitric oxide, TH1 cytokines, and other oxidative and inflammatory stimuli. [17][18][19] During acute oxidative stress-induced neurotoxicity, HO-1 has been shown to have cytoprotective effects; however, chronic expression of HO-1 has been proposed to be detrimental to cell health and survival.…”

Section: Introductionmentioning

confidence: 99%

Salivary Heme Oxygenase-1: A Potential Biomarker for Central Neurodegeneration

Galindez

Juwara

Cressatti

et al. 2021

J Cent Nerv Syst Dis

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Background: Parkinson disease (PD) is the second most common neurodegenerative disease, affecting 2% of the population over 65 years of age. PD diagnosis is based on clinical examination and can only be confirmed during autopsy. In 2018, we reported that heme oxygenase-1 (HO-1), an inducible stress response protein important for heme catabolism and implicated in PD pathology, was higher in PD saliva relative to healthy controls, suggesting that salivary HO-1 may serve as a potential biomarker of PD. Objectives: To ascertain whether HO-1 protein levels are elevated in PD saliva relative to degenerative neurological, non-degenerative neurological and healthy controls. Methodology: The study included 307 participants comprising 75 participants with idiopathic PD and 3 control groups: 162 non-neurological, 37 non-PD degenerative neurological, and 33 non-degenerative neurological participants. Salivary HO-1 and total protein concentrations were measured using ELISA and BCA assay, respectively. Receiver operating characteristic (ROC) curves were used to estimate model discrimination. Analyses were adjusted by age, sex, total protein, and relevant comorbidities. Results: Elevated HO-1 concentrations were observed in the PD group and other neurodegenerative conditions compared to subjects with no neurological or non-degenerative neurological conditions. ROC curves using HO-1 levels and covariates yielded areas under the curve above 85% in models for PD or neurodegenerative conditions versus controls. Conclusions: Salivary HO-1 concentrations in combination with covariates may provide a biomarker signature that distinguishes patients with neurodegenerative conditions from persons without. Classification of evidence: This study provides Class III evidence that salivary HO-1 multivariable models can distinguish neurodegenerative conditions.

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Salivary alpha-synuclein (total and oligomeric form): potential biomarkers in Parkinson’s disease

Cited by 20 publications

References 35 publications

Alpha-Synuclein as a Biomarker of Parkinson’s Disease: Good, but Not Good Enough

Alpha-Synuclein as a Biomarker of Parkinson’s Disease: Good, but Not Good Enough

Salivary Biomarkers: Future Approaches for Early Diagnosis of Neurodegenerative Diseases

Salivary Heme Oxygenase-1: A Potential Biomarker for Central Neurodegeneration

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