Alpha-Synuclein in Peripheral Tissues As a Possible Marker for Neurological Diseases and Other Medical Conditions

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2023 Aug 26

PMID 37627328

Authors

Felix Javier Jimenez-Jimenez

Hortensia Alonso-Navarro

Elena Garcia-Martin

Diego Santos-Garcia

Ivan Martinez-Valbuena

Jose A G Agundez

Affiliations

Soon will be listed here.

Abstract

The possible usefulness of alpha-synuclein (aSyn) determinations in peripheral tissues (blood cells, salivary gland biopsies, olfactory mucosa, digestive tract, skin) and in biological fluids, except for cerebrospinal fluid (serum, plasma, saliva, feces, urine), as a marker of several diseases, has been the subject of numerous publications. This narrative review summarizes data from studies trying to determine the role of total, oligomeric, and phosphorylated aSyn determinations as a marker of various diseases, especially PD and other alpha-synucleinopathies. In summary, the results of studies addressing the determinations of aSyn in its different forms in peripheral tissues (especially in platelets, skin, and digestive tract, but also salivary glands and olfactory mucosa), in combination with other potential biomarkers, could be a useful tool to discriminate PD from controls and from other causes of parkinsonisms, including synucleinopathies.

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References

Taraskina A, Filimonov V, Kozlovskaya Y, Morozova M, Gaschin D, Schwarzman A . High level of alpha-synuclein mRNA in peripheral lymphocytes of patients with alcohol dependence syndrome. Bull Exp Biol Med. 2009; 146(5):609-11. DOI: 10.1007/s10517-009-0345-1. View

Kuhn I, Rogosch T, Schindler T, Tackenberg B, Zemlin M, Maier R . Serum titers of autoantibodies against α-synuclein and tau in child- and adulthood. J Neuroimmunol. 2018; 315:33-39. DOI: 10.1016/j.jneuroim.2017.12.003. View

Moraitou M, Sotiroudis G, Papagiannakis N, Ferraz M, Xenakis A, Aerts J . a-Synuclein and lipids in erythrocytes of Gaucher disease carriers and patients before and after enzyme replacement therapy. PLoS One. 2023; 18(2):e0277602. PMC: 9897572. DOI: 10.1371/journal.pone.0277602. View

Stefani A, Iranzo A, Holzknecht E, Perra D, Bongianni M, Gaig C . Alpha-synuclein seeds in olfactory mucosa of patients with isolated REM sleep behaviour disorder. Brain. 2021; 144(4):1118-1126. DOI: 10.1093/brain/awab005. View

Melli G, Vacchi E, Biemmi V, Galati S, Staedler C, Ambrosini R . Cervical skin denervation associates with alpha-synuclein aggregates in Parkinson disease. Ann Clin Transl Neurol. 2018; 5(11):1394-1407. PMC: 6243385. DOI: 10.1002/acn3.669. View

Kuzkina A, Panzer C, Seger A, Schmitt D, Rossle J, Schreglmann S . Dermal Real-Time Quaking-Induced Conversion Is a Sensitive Marker to Confirm Isolated Rapid Eye Movement Sleep Behavior Disorder as an Early α-Synucleinopathy. Mov Disord. 2023; 38(6):1077-1082. DOI: 10.1002/mds.29340. View

Mazzetti S, Basellini M, Ferri V, Cassani E, Cereda E, Paolini M . α-Synuclein oligomers in skin biopsy of idiopathic and monozygotic twin patients with Parkinson's disease. Brain. 2020; 143(3):920-931. PMC: 7089656. DOI: 10.1093/brain/awaa008. View

Polymeropoulos M, Lavedan C, Leroy E, Ide S, Dehejia A, Dutra A . Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science. 1997; 276(5321):2045-7. DOI: 10.1126/science.276.5321.2045. View

Yu Z, Liu G, Li Y, Arkin E, Zheng Y, Feng T . Erythrocytic α-Synuclein Species for Parkinson's Disease Diagnosis and the Correlations With Clinical Characteristics. Front Aging Neurosci. 2022; 14:827493. PMC: 8850836. DOI: 10.3389/fnagi.2022.827493. View

10.

Kadak M, Cetin I, Tarakcioglu M, Ozer O, Kacar S, Cimen B . Low Serum Level α-Synuclein and Tau Protein in Autism Spectrum Disorder Compared to Controls. Neuropediatrics. 2015; 46(6):410-5. DOI: 10.1055/s-0035-1565273. View

11.

Shannon K, Keshavarzian A, Mutlu E, Dodiya H, Daian D, Jaglin J . Alpha-synuclein in colonic submucosa in early untreated Parkinson's disease. Mov Disord. 2011; 27(6):709-15. DOI: 10.1002/mds.23838. View

12.

Nuzhnyi E, Emelyanov A, Boukina T, Usenko T, Yakimovskii A, Zakharova E . Plasma oligomeric alpha-synuclein is associated with glucocerebrosidase activity in Gaucher disease. Mov Disord. 2015; 30(7):989-91. DOI: 10.1002/mds.26200. View

13.

Shalash A, Salama M, Makar M, Roushdy T, Elrassas H, Mohamed W . Elevated Serum α-Synuclein Autoantibodies in Patients with Parkinson's Disease Relative to Alzheimer's Disease and Controls. Front Neurol. 2018; 8:720. PMC: 5744443. DOI: 10.3389/fneur.2017.00720. View

14.

Gorostidi A, Bergareche A, Ruiz-Martinez J, Marti-Masso J, Cruz M, Varghese S . Αlpha-synuclein levels in blood plasma from LRRK2 mutation carriers. PLoS One. 2013; 7(12):e52312. PMC: 3531490. DOI: 10.1371/journal.pone.0052312. View

15.

Wijeyekoon R, Kronenberg-Versteeg D, Scott K, Hayat S, Kuan W, Evans J . Peripheral innate immune and bacterial signals relate to clinical heterogeneity in Parkinson's disease. Brain Behav Immun. 2020; 87:473-488. PMC: 7613010. DOI: 10.1016/j.bbi.2020.01.018. View

16.

Brighina L, Prigione A, Begni B, Galbussera A, Andreoni S, Piolti R . Lymphomonocyte alpha-synuclein levels in aging and in Parkinson disease. Neurobiol Aging. 2008; 31(5):884-5. DOI: 10.1016/j.neurobiolaging.2008.06.010. View

17.

Wang Z, Becker K, Donadio V, Siedlak S, Yuan J, Rezaee M . Skin α-Synuclein Aggregation Seeding Activity as a Novel Biomarker for Parkinson Disease. JAMA Neurol. 2020; . PMC: 7522783. DOI: 10.1001/jamaneurol.2020.3311. View

18.

Ikemura M, Saito Y, Sengoku R, Sakiyama Y, Hatsuta H, Kanemaru K . Lewy body pathology involves cutaneous nerves. J Neuropathol Exp Neurol. 2008; 67(10):945-53. DOI: 10.1097/NEN.0b013e318186de48. View

19.

Brudek T, Winge K, Folke J, Christensen S, Fog K, Pakkenberg B . Autoimmune antibody decline in Parkinson's disease and Multiple System Atrophy; a step towards immunotherapeutic strategies. Mol Neurodegener. 2017; 12(1):44. PMC: 5463400. DOI: 10.1186/s13024-017-0187-7. View

20.

Donadio V, Incensi A, Del Sorbo F, Rizzo G, Infante R, Scaglione C . Skin Nerve Phosphorylated α-Synuclein Deposits in Parkinson Disease With Orthostatic Hypotension. J Neuropathol Exp Neurol. 2018; 77(10):942-949. DOI: 10.1093/jnen/nly074. View