Increased alpha-synuclein tear fluid levels in patients with Parkinson’s disease

Maass, Fabian; Rikker, Sebastian; Dambeck, Vivian; Warth, Carmina; Tatenhorst, Lars; Csóti, Ilona; Schmitz, Matthias; Zerr, Inga; Leha, Andreas; Bähr, Mathias; Lingor, Paul

doi:10.1038/s41598-020-65503-1

Cited by 32 publications

(35 citation statements)

References 20 publications

(25 reference statements)

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“…α‐Syn is a cytosolic protein that lacks a secretory signal peptide sequence. Previous studies have reported that α‐syn is detected in the extracellular compartments, including the cerebrospinal fluid [15,16], plasma [16,17], saliva [18], tears [19], and urine [20] in both healthy controls and patients with PD. Additionally, α‐syn exists in various forms, including monomeric, oligomeric, and phosphorylated forms [17,21].…”

Section: α‐Syn Species Are Released From the Cells Through Various Mechanismsmentioning

confidence: 99%

Molecular events underlying the cell‐to‐cell transmission of α‐synuclein

Choi

Park

2020

The FEBS Journal

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The pathogenesis of Parkinson's disease (PD), which is a progressive neurodegenerative disease, is associated with the formation of protein inclusion bodies called Lewy bodies (LB) or Lewy neurites (LN). α‐Synuclein (α‐Syn) is a major component of LB and LN. The formation of LB or LN is mediated by formation of α‐Syn fibrils, which are formed from α‐Syn monomers and oligomers. Additionally, intercellular α‐Syn propagation has been proposed to be important for the progression of PD. Thus, various studies have focused on elucidating the role of α‐Syn propagation in the pathogenesis of PD. Previous studies have reported that α‐Syn species are released from the cells through various pathways, including the unconventional secretion pathways. The released α‐Syn species are internalized by the cells through multiple mechanisms, including receptor‐mediated endocytosis. Some molecular processes involved in intercellular α‐Syn propagation have been recently elucidated. This review discusses the current studies on the molecular mechanisms underlying the release and uptake of α‐Syn and their physiological relevance.

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Section: α‐Syn Species Are Released From the Cells Through Various Mechanismsmentioning

confidence: 99%

Molecular events underlying the cell‐to‐cell transmission of α‐synuclein

Choi

Park

2020

The FEBS Journal

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“…As the ultrasensitive methods, SMTs can contribute to driving this process. Recently, the presence of α -syn in saliva and tears has been proposed as the new potential biofluid biomarkers for PD diagnosis (Devic et al ., 2011; Maass et al ., 2020). Although their clinical feasibilities need more verification, SMTs provide the possibility to detect the low concentrations of heterogeneous amyloid aggregates.…”

Section: Application Of Smts For Amyloidosis Diagnosismentioning

confidence: 99%

Single-molecule studies of amyloid proteins: from biophysical properties to diagnostic perspectives

Cao

Loch

et al. 2020

Quart. Rev. Biophys.

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In neurodegenerative diseases, a wide range of amyloid proteins or peptides such as amyloid-beta and α-synuclein fail to keep native functional conformations, followed by misfolding and self-assembling into a diverse array of aggregates. The aggregates further exert toxicity leading to the dysfunction, degeneration and loss of cells in the affected organs. Due to the disordered structure of the amyloid proteins, endogenous molecules, such as lipids, are prone to interact with amyloid proteins at a low concentration and influence amyloid cytotoxicity. The heterogeneity of amyloid proteinscomplicates the understanding of the amyloid cytotoxicity when relying only on conventional bulk and ensemble techniques. As complementary tools, single-molecule techniques (SMTs) provide novel insights into the different subpopulations of a heterogeneous amyloid mixture as well as the cytotoxicity, in particular as involved in lipid membranes. This review focuses on the recent advances of a series of SMTs, including single-molecule fluorescence imaging, single-molecule force spectroscopy and single-nanopore electrical recording, for the understanding of the amyloid molecular mechanism. The working principles, benefits and limitations of each technique are discussed and compared in amyloid protein related studies.. We also discuss why SMTs show great potential and are worthy of further investigation with feasibility studies as diagnostic tools of neurodegenerative diseases and which limitations are to be addressed.

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“…Another study analyzed the altered level of alpha-synuclein in tear fluid obtained from 75 PD patients, 75 healthy controls, and 31 atypical Parkinsonian patients with an ultra-sensitive single-molecule array (SIMOA) system and human alpha-synuclein immunoassay. Levels of total soluble alpha-synuclein in PD were significantly increased versus control subjects (p = 0.03; area under curve (AUC) PD versus controls 0.60) [182]. Alphasynuclein could be detected and quantified in tears (small but significant differences) between PD and control subjects.…”

Section: Parkinson's Diseasementioning

confidence: 88%

“…Alphasynuclein could be detected and quantified in tears (small but significant differences) between PD and control subjects. Alpha-synuclein can be used as a promising source for further study of PD biomarker [182].…”

Section: Parkinson's Diseasementioning

confidence: 99%

Mass spectrometry analysis of human tear fluid biomarkers specific for ocular and systemic diseases in the context of 3P medicine

Zhan

Guo

et al. 2021

EPMA Journal

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Over the last two decades, a large number of non-communicable/chronic disorders reached an epidemic level on a global scale such as diabetes mellitus type 2, cardio-vascular disease, several types of malignancies, neurological and eye pathologies—all exerted system’s enormous socio-economic burden to primary, secondary, and tertiary healthcare. The paradigm change from reactive to predictive, preventive, and personalized medicine (3PM/PPPM) has been declared as an essential transformation of the overall healthcare approach to benefit the patient and society at large. To this end, specific biomarker panels are instrumental for a cost-effective predictive approach of individualized prevention and treatments tailored to the person. The source of biomarkers is crucial for specificity and reliability of diagnostic tests and treatment targets. Furthermore, any diagnostic approach preferentially should be noninvasive to increase availability of the biomaterial, and to decrease risks of potential complications as well as concomitant costs. These requirements are clearly fulfilled by tear fluid, which represents a precious source of biomarker panels. The well-justified principle of a “sick eye in a sick body” makes comprehensive tear fluid biomarker profiling highly relevant not only for diagnostics of eye pathologies but also for prediction, prognosis, and treatment monitoring of systemic diseases. One prominent example is the Sicca syndrome linked to a cascade of severe complications that include dry eye, neurologic, and oncologic diseases. In this review, protein profiles in tear fluid are highlighted and corresponding biomarkers are exemplified for several relevant pathologies, including dry eye disease, diabetic retinopathy, cancers, and neurological disorders. Corresponding analytical approaches such as sample pre-processing, differential proteomics, electrophoretic techniques, high-performance liquid chromatography (HPLC), enzyme-linked immuno-sorbent assay (ELISA), microarrays, and mass spectrometry (MS) methodology are detailed. Consequently, we proposed the overall strategies based on the tear fluid biomarkers application for 3P medicine practice. In the context of 3P medicine, tear fluid analytical pathways are considered to predict disease development, to target preventive measures, and to create treatment algorithms tailored to individual patient profiles.

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Increased alpha-synuclein tear fluid levels in patients with Parkinson’s disease

Cited by 32 publications

References 20 publications

Molecular events underlying the cell‐to‐cell transmission of α‐synuclein

Molecular events underlying the cell‐to‐cell transmission of α‐synuclein

Single-molecule studies of amyloid proteins: from biophysical properties to diagnostic perspectives

Mass spectrometry analysis of human tear fluid biomarkers specific for ocular and systemic diseases in the context of 3P medicine

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