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Mechanistic Insight into Intestinal α-Synuclein Aggregation in Parkinson's Disease Using a Laser-Printed Electrochemical Sensor.

التفاصيل البيبلوغرافية
العنوان: Mechanistic Insight into Intestinal α-Synuclein Aggregation in Parkinson's Disease Using a Laser-Printed Electrochemical Sensor.
المؤلفون: Balsamo JM; Department of Chemistry, University of California, Irvine, California 92617, United States., Zhou K; School of Electrical Engineering and Computer Science, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.; Materials Research Institute, The Pennsylvania State University, University Park, Pennsylvania 16802, United States., Kammarchedu V; School of Electrical Engineering and Computer Science, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.; Materials Research Institute, The Pennsylvania State University, University Park, Pennsylvania 16802, United States., Ebrahimi A; School of Electrical Engineering and Computer Science, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.; Materials Research Institute, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.; Department of Biomedical Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802, United States., Bess EN; Department of Chemistry, University of California, Irvine, California 92617, United States.; Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92617, United States.
المصدر: ACS chemical neuroscience [ACS Chem Neurosci] 2024 Jul 17; Vol. 15 (14), pp. 2623-2632. Date of Electronic Publication: 2024 Jul 03.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101525337 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1948-7193 (Electronic) Linking ISSN: 19487193 NLM ISO Abbreviation: ACS Chem Neurosci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Chemical Society
مواضيع طبية MeSH: alpha-Synuclein*/metabolism , Parkinson Disease*/metabolism, Humans ; Dopamine/metabolism ; Electrochemical Techniques/methods ; Enteroendocrine Cells/metabolism ; Gastrointestinal Microbiome/physiology ; Lasers
مستخلص: Aggregated deposits of the protein α-synuclein and depleting levels of dopamine in the brain correlate with Parkinson's disease development. Treatments often focus on replenishing dopamine in the brain; however, the brain might not be the only site requiring attention. Aggregates of α-synuclein appear to accumulate in the gut years prior to the onset of any motor symptoms. Enteroendocrine cells (specialized gut epithelial cells) may be the source of intestinal α-synuclein, as they natively express this protein. Enteroendocrine cells are constantly exposed to gut bacteria and their metabolites because they border the gut lumen. These cells also express the dopamine metabolic pathway and form synapses with vagal neurons, which innervate the gut and brain. Through this connection, Parkinson's disease pathology may originate in the gut and spread to the brain over time. Effective therapeutics to prevent this disease progression are lacking due to a limited understanding of the mechanisms by which α-synuclein aggregation occurs in the gut. We previously proposed a gut bacterial metabolic pathway responsible for the initiation of α-synuclein aggregation that is dependent on the oxidation of dopamine. Here, we develop a new tool, a laser-induced graphene-based electrochemical sensor chip, to track α-synuclein aggregation and dopamine level over time. Using these sensor chips, we evaluated diet-derived catechols dihydrocaffeic acid and caffeic acid as potential inhibitors of α-synuclein aggregation. Our results suggest that these molecules inhibit dopamine oxidation. We also found that these dietary catechols inhibit α-synuclein aggregation in STC-1 enteroendocrine cells. These findings are critical next steps to reveal new avenues for targeted therapeutics to treat Parkinson's disease, specifically in the context of functional foods that may be used to reshape the gut environment.
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فهرسة مساهمة: Keywords: LIG sensor; Parkinson’s disease; dopamine; iron; polyphenols; α-synuclein
المشرفين على المادة: 0 (alpha-Synuclein)
VTD58H1Z2X (Dopamine)
0 (SNCA protein, human)
تواريخ الأحداث: Date Created: 20240703 Date Completed: 20240717 Latest Revision: 20240722
رمز التحديث: 20240722
مُعرف محوري في PubMed: PMC11258680
DOI: 10.1021/acschemneuro.4c00106
PMID: 38959406
قاعدة البيانات: MEDLINE
الوصف
تدمد:1948-7193
DOI:10.1021/acschemneuro.4c00106