دورية أكاديمية
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Discovery of a Gut Bacterial Metabolic Pathway that Drives α-Synuclein Aggregation.

التفاصيل البيبلوغرافية
العنوان: Discovery of a Gut Bacterial Metabolic Pathway that Drives α-Synuclein Aggregation.
المؤلفون: Ortiz de Ora L; Department of Chemistry, University of California, Irvine, California 92617, United States., Balsamo JM; Department of Chemistry, University of California, Irvine, California 92617, United States., Uyeda KS; Department of Chemistry, University of California, Irvine, California 92617, 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 biology [ACS Chem Biol] 2024 Apr 19; Vol. 19 (4), pp. 1011-1021. Date of Electronic Publication: 2024 Mar 22.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101282906 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1554-8937 (Electronic) Linking ISSN: 15548929 NLM ISO Abbreviation: ACS Chem Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Chemical Society, c2006-
مواضيع طبية MeSH: alpha-Synuclein*/metabolism , Escherichia coli K12*/metabolism , Gastrointestinal Microbiome* , Parkinson Disease*/metabolism , Parkinson Disease*/microbiology , Protein Aggregates*, Humans ; Dopamine/analogs & derivatives ; Metabolic Networks and Pathways ; Nitrates/metabolism ; Nitrites/metabolism ; Enterobacteriaceae/metabolism
مستخلص: Parkinson's disease (PD) etiology is associated with aggregation and accumulation of α-synuclein (α-syn) proteins in midbrain dopaminergic neurons. Emerging evidence suggests that in certain subtypes of PD, α-syn aggregates originate in the gut and subsequently spread to the brain. However, mechanisms that instigate α-syn aggregation in the gut have remained elusive. In the brain, the aggregation of α-syn is induced by oxidized dopamine. Such a mechanism has not been explored in the context of the gastrointestinal tract, a niche harboring 46% of the body's dopamine reservoirs. Here, we report that Enterobacteriaceae , a bacterial family prevalent in human gut microbiotas, induce α-syn aggregation. More specifically, our in vitro data indicate that respiration of nitrate by Escherichia coli K-12, which results in production of nitrite that mediates oxidation of Fe 2+ to Fe 3+ , creates an oxidizing redox potential. These oxidizing conditions enabled the formation of dopamine-derived quinones and α-syn aggregates. Exposing nitrite, but not nitrate, to enteroendocrine STC-1 cells induced aggregation of α-syn that is natively expressed in these cells, which line the intestinal tract. Taken together, our findings indicate that bacterial nitrate reduction may be critical for initiating intestinal α-syn aggregation.
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معلومات مُعتمدة: P30 CA062203 United States CA NCI NIH HHS; P50 GM076516 United States GM NIGMS NIH HHS
المشرفين على المادة: 0 (alpha-Synuclein)
VTD58H1Z2X (Dopamine)
50673-96-6 (dopamine quinone)
0 (Nitrates)
0 (Nitrites)
0 (Protein Aggregates)
تواريخ الأحداث: Date Created: 20240322 Date Completed: 20240422 Latest Revision: 20240613
رمز التحديث: 20240614
مُعرف محوري في PubMed: PMC11040608
DOI: 10.1021/acschembio.4c00095
PMID: 38517270
قاعدة البيانات: MEDLINE
الوصف
تدمد:1554-8937
DOI:10.1021/acschembio.4c00095