دورية أكاديمية
أعرض في EDS

Octopamine metabolically reprograms astrocytes to confer neuroprotection against α-synuclein.

التفاصيل البيبلوغرافية
العنوان: Octopamine metabolically reprograms astrocytes to confer neuroprotection against α-synuclein.
المؤلفون: Shum A; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611., Zaichick S; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611., McElroy GS; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611., D'Alessandro K; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611., Alasady MJ; Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611., Novakovic M; Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago IL 60611., Peng W; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611., Grebenik EA; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611., Chung D; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611., Flanagan ME; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago IL 60611.; Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University Fienberg School of Medicine, Chicago IL 60611., Smith R; Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611., Morales A; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611., Stumpf L; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611., McGrath K; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611., Krainc D; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611., Mendillo ML; Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611., Prakriya M; Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago IL 60611., Chandel NS; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611., Caraveo G; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611.
المصدر: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2023 Apr 25; Vol. 120 (17), pp. e2217396120. Date of Electronic Publication: 2023 Apr 17.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : National Academy of Sciences
مواضيع طبية MeSH: alpha-Synuclein*/metabolism , Octopamine*/metabolism, Animals ; Astrocytes/metabolism ; Calcineurin/metabolism ; Lactates/metabolism ; Mammals/metabolism ; Neuroprotection ; Neurotransmitter Agents/metabolism
مستخلص: Octopamine is a well-established invertebrate neurotransmitter involved in fight or flight responses. In mammals, its function was replaced by epinephrine. Nevertheless, it is present at trace amounts and can modulate the release of monoamine neurotransmitters by a yet unidentified mechanism. Here, through a multidisciplinary approach utilizing in vitro and in vivo models of α-synucleinopathy, we uncovered an unprecedented role for octopamine in driving the conversion from toxic to neuroprotective astrocytes in the cerebral cortex by fostering aerobic glycolysis. Physiological levels of neuron-derived octopamine act on astrocytes via a trace amine-associated receptor 1-Orai1-Ca 2+ -calcineurin-mediated signaling pathway to stimulate lactate secretion. Lactate uptake in neurons via the monocarboxylase transporter 2-calcineurin-dependent pathway increases ATP and prevents neurodegeneration. Pathological increases of octopamine caused by α-synuclein halt lactate production in astrocytes and short-circuits the metabolic communication to neurons. Our work provides a unique function of octopamine as a modulator of astrocyte metabolism and subsequent neuroprotection with implications to α-synucleinopathies.
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معلومات مُعتمدة: K08 AG065463 United States AG NIA NIH HHS; P30 AG066546 United States AG NIA NIH HHS; R01 NS117750 United States NS NINDS NIH HHS; RF1 AG072080 United States AG NIA NIH HHS
فهرسة مساهمة: Keywords: astrocytes; calcineurin; lactate; octopamine; synuclein
المشرفين على المادة: 0 (alpha-Synuclein)
EC 3.1.3.16 (Calcineurin)
0 (Lactates)
0 (Neurotransmitter Agents)
14O50WS8JD (Octopamine)
تواريخ الأحداث: Date Created: 20230417 Date Completed: 20230509 Latest Revision: 20240425
رمز التحديث: 20240425
مُعرف محوري في PubMed: PMC10151466
DOI: 10.1073/pnas.2217396120
PMID: 37068235
قاعدة البيانات: MEDLINE
الوصف
تدمد:1091-6490
DOI:10.1073/pnas.2217396120