Octopamine metabolically reprograms astrocytes to confer neuroprotection against α-synuclein
| العنوان: | Octopamine metabolically reprograms astrocytes to confer neuroprotection against α-synuclein |
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| المؤلفون: | Andrew Shum, Sofia Zaichick, Gregory S. McElroy, Karis D’Alessandro, Michaela Novakovic, Wesley Peng, Daayun Chung, Margaret E. Flanagan, Roger Smith, Alejandro Morales, Laetitia Stumpf, Kaitlyn McGrath, Dimitri Krainc, Marc L. Mendillo, Murali Prakriya, Navdeep S. Chandel, Gabriela Caraveo |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2022. |
| سنة النشر: | 2022 |
| الوصف: | Octopamine is a well-established invertebrate neurotransmitter involved in fight-or-flight responses. In mammals, its function was replaced by norepinephrine. 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 TAAR1-Orai1-Ca2+-calcineurin-mediated signaling pathway to stimulate lactate secretion. Lactate uptake in neurons via the MCT2-calcineurin-dependent pathway increases ATP and prevents neurodegeneration. Pathological increases of octopamine caused by α-synuclein halts lactate production in astrocytes and short-circuits the metabolic communication to neurons. Our work provides a novel function of octopamine as a modulator of astrocyte metabolism and subsequent neuroprotection with implications to α-synucleinopathies. |
| DOI: | 10.1101/2022.10.04.510813 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::6b3f7497dbd2ad211a865d6b8b07e489 https://doi.org/10.1101/2022.10.04.510813 |
| رقم الانضمام: | edsair.doi...........6b3f7497dbd2ad211a865d6b8b07e489 |
| قاعدة البيانات: | OpenAIRE |
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