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- Publisher Website: 10.1016/j.celrep.2024.113865
- Scopus: eid_2-s2.0-85186749980
- PMID: 38412096
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Article: Metabolic rescue of α-synuclein-induced neurodegeneration through propionate supplementation and intestine-neuron signaling in C. elegans
Title | Metabolic rescue of α-synuclein-induced neurodegeneration through propionate supplementation and intestine-neuron signaling in C. elegans |
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Authors | |
Keywords | C. elegans CP: Metabolism CP: Neuroscience energy production gut-brain axis mitochondrial unfolded protein response mitoUPR neurodegeneration Parkinson's disease propionate SCFAs short-chain fatty acids vitamin B12 α-synuclein |
Issue Date | 26-Mar-2024 |
Publisher | Cell Press |
Citation | Cell Reports, 2024, v. 43, n. 3 How to Cite? |
Abstract | Microbial metabolites that can modulate neurodegeneration are promising therapeutic targets. Here, we found that the short-chain fatty acid propionate protects against α-synuclein-induced neuronal death and locomotion defects in a Caenorhabditis elegans model of Parkinson's disease (PD) through bidirectional regulation between the intestine and neurons. Both depletion of dietary vitamin B12, which induces propionate breakdown, and propionate supplementation suppress neurodegeneration and reverse PD-associated transcriptomic aberrations. Neuronal α-synuclein aggregation induces intestinal mitochondrial unfolded protein response (mitoUPR), which leads to reduced propionate levels that trigger transcriptional reprogramming in the intestine and cause defects in energy production. Weakened intestinal metabolism exacerbates neurodegeneration through interorgan signaling. Genetically enhancing propionate production or overexpressing metabolic regulators downstream of propionate in the intestine rescues neurodegeneration, which then relieves mitoUPR. Importantly, propionate supplementation suppresses neurodegeneration without reducing α-synuclein aggregation, demonstrating metabolic rescue of neuronal proteotoxicity downstream of protein aggregates. Our study highlights the involvement of small metabolites in the gut-brain interaction in neurodegenerative diseases. |
Persistent Identifier | http://hdl.handle.net/10722/347462 |
ISSN |
DC Field | Value | Language |
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dc.contributor.author | Wang, Chenyin | - |
dc.contributor.author | Yang, Meigui | - |
dc.contributor.author | Liu, Dongyao | - |
dc.contributor.author | Zheng, Chaogu | - |
dc.date.accessioned | 2024-09-23T03:11:04Z | - |
dc.date.available | 2024-09-23T03:11:04Z | - |
dc.date.issued | 2024-03-26 | - |
dc.identifier.citation | Cell Reports, 2024, v. 43, n. 3 | - |
dc.identifier.issn | 2639-1856 | - |
dc.identifier.uri | http://hdl.handle.net/10722/347462 | - |
dc.description.abstract | <p>Microbial metabolites that can modulate neurodegeneration are promising therapeutic targets. Here, we found that the short-chain fatty acid propionate protects against α-synuclein-induced neuronal death and locomotion defects in a Caenorhabditis elegans model of Parkinson's disease (PD) through bidirectional regulation between the intestine and neurons. Both depletion of dietary vitamin B12, which induces propionate breakdown, and propionate supplementation suppress neurodegeneration and reverse PD-associated transcriptomic aberrations. Neuronal α-synuclein aggregation induces intestinal mitochondrial unfolded protein response (mitoUPR), which leads to reduced propionate levels that trigger transcriptional reprogramming in the intestine and cause defects in energy production. Weakened intestinal metabolism exacerbates neurodegeneration through interorgan signaling. Genetically enhancing propionate production or overexpressing metabolic regulators downstream of propionate in the intestine rescues neurodegeneration, which then relieves mitoUPR. Importantly, propionate supplementation suppresses neurodegeneration without reducing α-synuclein aggregation, demonstrating metabolic rescue of neuronal proteotoxicity downstream of protein aggregates. Our study highlights the involvement of small metabolites in the gut-brain interaction in neurodegenerative diseases.</p> | - |
dc.language | eng | - |
dc.publisher | Cell Press | - |
dc.relation.ispartof | Cell Reports | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | C. elegans | - |
dc.subject | CP: Metabolism | - |
dc.subject | CP: Neuroscience | - |
dc.subject | energy production | - |
dc.subject | gut-brain axis | - |
dc.subject | mitochondrial unfolded protein response | - |
dc.subject | mitoUPR | - |
dc.subject | neurodegeneration | - |
dc.subject | Parkinson's disease | - |
dc.subject | propionate | - |
dc.subject | SCFAs | - |
dc.subject | short-chain fatty acids | - |
dc.subject | vitamin B12 | - |
dc.subject | α-synuclein | - |
dc.title | Metabolic rescue of α-synuclein-induced neurodegeneration through propionate supplementation and intestine-neuron signaling in C. elegans | - |
dc.type | Article | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1016/j.celrep.2024.113865 | - |
dc.identifier.pmid | 38412096 | - |
dc.identifier.scopus | eid_2-s2.0-85186749980 | - |
dc.identifier.volume | 43 | - |
dc.identifier.issue | 3 | - |
dc.identifier.eissn | 2211-1247 | - |
dc.identifier.issnl | 2211-1247 | - |