A novel super-resolution microscopy platform for cutaneous alpha-synuclein detection in Parkinson's disease.

Autor:	Sade O; School of Neurobiology, Biochemistry, Biophysics, Life Sciences Faculty, Tel Aviv University, Tel Aviv, Israel., Fischel D; School of Neurobiology, Biochemistry, Biophysics, Life Sciences Faculty, Tel Aviv University, Tel Aviv, Israel.; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel., Barak-Broner N; School of Neurobiology, Biochemistry, Biophysics, Life Sciences Faculty, Tel Aviv University, Tel Aviv, Israel., Halevi S; School of Neurobiology, Biochemistry, Biophysics, Life Sciences Faculty, Tel Aviv University, Tel Aviv, Israel.; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel., Gottfried I; School of Neurobiology, Biochemistry, Biophysics, Life Sciences Faculty, Tel Aviv University, Tel Aviv, Israel., Bar-On D; School of Neurobiology, Biochemistry, Biophysics, Life Sciences Faculty, Tel Aviv University, Tel Aviv, Israel.; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel., Sachs S; Department of Biotechnology and Biophysics, Biocenter, University of Würzburg, Würzburg, Germany., Mirelman A; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.; Movement Disorders Division, Neurological Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.; Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel., Thaler A; Movement Disorders Division, Neurological Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.; Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel., Gour A; Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.; Department of Neurology, Meir Medical Center, Kfar Saba, Israel., Kestenbaum M; Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.; Department of Neurology, Meir Medical Center, Kfar Saba, Israel., Gana Weisz M; Movement Disorders Division, Neurological Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel., Anis S; Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.; Department of Neurology, Movement Disorders Institute, Chaim Sheba Medical Center, Ramat Gan, Israel., Soto C; Mitchell Center for Alzheimer's Disease and Related Brain Disorders, University of Texas Medical School, Houston, TX, United States., Roitman MS; Department of Neurology, Movement Disorders Institute, Chaim Sheba Medical Center, Ramat Gan, Israel., Shahar S; Department of Statistics, Exact Sciences Faculty, Tel Aviv University, Tel Aviv, Israel., Doppler K; Department of Neurology, University Hospital Würzburg, Würzburg, Germany., Sauer M; Department of Biotechnology and Biophysics, Biocenter, University of Würzburg, Würzburg, Germany., Giladi N; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.; Movement Disorders Division, Neurological Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.; Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel., Lev N; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.; Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.; Department of Neurology, Meir Medical Center, Kfar Saba, Israel., Alcalay RN; Movement Disorders Division, Neurological Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.; Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel., Hassin-Baer S; Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.; Department of Neurology, Movement Disorders Institute, Chaim Sheba Medical Center, Ramat Gan, Israel., Ashery U; School of Neurobiology, Biochemistry, Biophysics, Life Sciences Faculty, Tel Aviv University, Tel Aviv, Israel.; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Jazyk:	angličtina
Zdroj:	Frontiers in molecular neuroscience [Front Mol Neurosci] 2024 Sep 04; Vol. 17, pp. 1431549. Date of Electronic Publication: 2024 Sep 04 (Print Publication: 2024).
DOI:	10.3389/fnmol.2024.1431549
Abstrakt:	Alpha-synuclein (aSyn) aggregates in the central nervous system are the main pathological hallmark of Parkinson's disease (PD). ASyn aggregates have also been detected in many peripheral tissues, including the skin, thus providing a novel and accessible target tissue for the detection of PD pathology. Still, a well-established validated quantitative biomarker for early diagnosis of PD that also allows for tracking of disease progression remains lacking. The main goal of this research was to characterize aSyn aggregates in skin biopsies as a comparative and quantitative measure for PD pathology. Using direct stochastic optical reconstruction microscopy ( d STORM) and computational tools, we imaged total and phosphorylated-aSyn at the single molecule level in sweat glands and nerve bundles of skin biopsies from healthy controls (HCs) and PD patients. We developed a user-friendly analysis platform that offers a comprehensive toolkit for researchers that combines analysis algorithms and applies a series of cluster analysis algorithms (i.e., DBSCAN and FOCAL) onto d STORM images. Using this platform, we found a significant decrease in the ratio of the numbers of neuronal marker molecules to phosphorylated-aSyn molecules, suggesting the existence of damaged nerve cells in fibers highly enriched with phosphorylated-aSyn molecules. Furthermore, our analysis found a higher number of aSyn aggregates in PD subjects than in HC subjects, with differences in aggregate size, density, and number of molecules per aggregate. On average, aSyn aggregate radii ranged between 40 and 200 nm and presented an average density of 0.001-0.1 molecules/nm 2 . Our d STORM analysis thus highlights the potential of our platform for identifying quantitative characteristics of aSyn distribution in skin biopsies not previously described for PD patients while offering valuable insight into PD pathology by elucidating patient aSyn aggregation status. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Sade, Fischel, Barak-Broner, Halevi, Gottfried, Bar-On, Sachs, Mirelman, Thaler, Gour, Kestenbaum, Gana Weisz, Anis, Soto, Roitman, Shahar, Doppler, Sauer, Giladi, Lev, Alcalay, Hassin-Baer, and Ashery.)
Databáze:	MEDLINE
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