4.7 Article

A rare natural lipid induces neuroglobin expression to prevent amyloid oligomers toxicity and retinal neurodegeneration

Journal

AGING CELL
Volume 21, Issue 7, Pages -

Publisher

WILEY
DOI: 10.1111/acel.13645

Keywords

amyloid; neurodegeneration; neuroglobin; neuroprotection; protein aggregation; tripentadecanoin; yeast aging; Yhb1

Funding

  1. Academy of Finland [317038, 319907]
  2. Biotechnology and Biological Sciences Research Council [BB/S001204/1]
  3. Sigrid Juseliuksen Saatio
  4. Academy of Finland (AKA) [319907, 317038, 319907, 317038] Funding Source: Academy of Finland (AKA)

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This study found that the natural lipid tripentadecanoin can delay the formation of protein aggregates and extend cellular lifespan, offering a potential treatment for neurodegenerative diseases. Tripentadecanoin can also protect neurons from amyloid toxicity and promote the recovery of retinal cells.
Most neurodegenerative diseases such as Alzheimer's disease are proteinopathies linked to the toxicity of amyloid oligomers. Treatments to delay or cure these diseases are lacking. Using budding yeast, we report that the natural lipid tripentadecanoin induces expression of the nitric oxide oxidoreductase Yhb1 to prevent the formation of protein aggregates during aging and extends replicative lifespan. In mammals, tripentadecanoin induces expression of the Yhb1 orthologue, neuroglobin, to protect neurons against amyloid toxicity. Tripentadecanoin also rescues photoreceptors in a mouse model of retinal degeneration and retinal ganglion cells in a Rhesus monkey model of optic atrophy. Together, we propose that tripentadecanoin affects p-bodies to induce neuroglobin expression and offers a potential treatment for proteinopathies and retinal neurodegeneration.

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