2023
DOI: 10.1101/2023.01.10.523171
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MANF stimulates autophagy and restores mitochondrial homeostasis to treat toxic proteinopathy

Abstract: Misfolded protein aggregates may cause toxic proteinopathy, including autosomal dominant tubulointerstitial kidney disease due to uromodulin mutations (ADTKD-UMOD), one of the leading hereditary kidney diseases, and Alzheimer disease etc. There are no targeted therapies. ADTKD is also a genetic form of renal fibrosis and chronic kidney disease, which affects 500 million people worldwide. For the first time, in our newly generated mouse model recapitulating human ADTKD-UMOD carrying a leading UMOD deletion muta… Show more

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Cited by 1 publication
(2 citation statements)
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References 61 publications
(69 reference statements)
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“…We found that MANF-1 OE animals had reduced LGG-1::GFP and SQST-1::GFP puncta, suggesting that MANF-1 promotes autophagy. Consistent with these data, a recent study reported that MANF overexpression in mouse kidney cells promoted autophagy and mitochondrial biogenesis (Yeawon Kim et al 2023). The authors also observed a decrease in p62 abundance and identified p-AMPK and FOXO3 playing roles in promoting mitochondrial biogenesis.…”
Section: Discussionsupporting
confidence: 65%
See 1 more Smart Citation
“…We found that MANF-1 OE animals had reduced LGG-1::GFP and SQST-1::GFP puncta, suggesting that MANF-1 promotes autophagy. Consistent with these data, a recent study reported that MANF overexpression in mouse kidney cells promoted autophagy and mitochondrial biogenesis (Yeawon Kim et al 2023). The authors also observed a decrease in p62 abundance and identified p-AMPK and FOXO3 playing roles in promoting mitochondrial biogenesis.…”
Section: Discussionsupporting
confidence: 65%
“…6B), there was a significant reduction in LGG-1::GFP and SQST-1::GFP fluorescent puncta in seam cells and pharynx, respectively (Fig. 6C&F, D&G), consistent with increased autophagic clearance (Yeawon Kim et al 2023). We concluded that beneficial effects of MANF-1 overexpression are mediated through enhanced autophagy and lysosomal function.…”
Section: Manf-1 Promotes Autophagy and Lysosome Functionmentioning
confidence: 62%