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 PMID:37473700  

Neuron-specific proteasome activation exerts cell non-autonomous protection against amyloid-beta (Aβ) proteotoxicity in Caenorhabditis elegans.

Eleni Panagiotidou | Anna Gioran | Daniele Bano | Niki Chondrogianni
Redox biology | 2023

Proteostasis reinforcement is a promising approach in the design of therapeutic interventions against proteinopathies, including Alzheimer's disease. Understanding how and which parts of the proteostasis network should be enhanced is crucial in developing efficient therapeutic strategies. The ability of specific tissues to induce proteostatic responses in distal ones (cell non-autonomous regulation of proteostasis) is attracting interest. Although the proteasome is a major protein degradation node, nothing is known on its cell non-autonomous regulation. We show that proteasome activation in the nervous system can enhance the proteasome activity in the muscle of Caenorhabditis elegans. Mechanistically, this communication depends on Small Clear Vesicles, with glutamate as one of the neurotransmitters required for the distal regulation. More importantly, we demonstrate that this cell non-autonomous proteasome activation is translated into efficient prevention of amyloid-beta (Αβ)-mediated proteotoxic effects in the muscle of C. elegans but notably not to resistance against oxidative stress. Our in vivo data establish a mechanistic link between neuronal proteasome reinforcement and decreased Aβ proteotoxicity in the muscle. The identified distal communication may have serious implications in the design of therapeutic strategies based on tissue-specific proteasome manipulation.

Pubmed ID: 37473700

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This is a list of tools and resources that we have found mentioned in this publication.


Caenorhabditis Genetics Center (tool)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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KR1787 (organism)

RRID:WB-STRAIN:WBStrain00023941

Caenorhabditis elegans with name unc-13(e51) I. from WB.

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CB246 (organism)

RRID:WB-STRAIN:WBStrain00004134

Caenorhabditis elegans with name unc-64 (e246) III from WB.

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GMC101 (organism)

RRID:WB-STRAIN:WBStrain00007866

Caenorhabditis elegans with name [(Punc-54::A-beta::unc-54 3Prime UTR; Pmtl2::GFP)] from WB.

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YD114 (organism)

RRID:WB-STRAIN:WBStrain00049246

Caenorhabditis elegans with name EMPTY from WB.

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CL4176 (organism)

RRID:WB-STRAIN:WBStrain00005113

Caenorhabditis elegans with name smg-1(cc546ts); dvIs27 [Pmyo-3::human Amyloid beta 1-42; let-851 3'UTR; rol-6(su1006)] from WB.

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DLM9 (organism)

RRID:WB-STRAIN:WBStrain00005846

Caenorhabditis elegans with name ttTi5605 II; unc-119(ed3) III; uwaEx5. from WB.

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CB928 (organism)

RRID:WB-STRAIN:WBStrain00004215

Caenorhabditis elegans with name unc-31(e928) IV. from WB.

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N2 (organism)

RRID:WB-STRAIN:WBStrain00000001

Caenorhabditis elegans with name Caenorhabditis elegans wild isolate. from WB.

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