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Posted On: 11/15/2024 11:08:25 AM
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2x forthcoming MANF in Kidney Disease from WashUSTL. Focus is on Autosomal dominant tubulointerstitial kidney disease due to uromodulin mutations (ADTKD-UMOD). But I want to key in on something. Besides Dr. Urano's Lab, we now have an entirely separate lab, the Dr. Maggie Chen Lab, that's now demonstrating a nearly decade long commitment to MANF research - this time focused on the kidneys. Of course this adds to other labs internationally in China or like Dr. Saarma's lab in Finland. https://maggiechenlab.wustl.edu/
Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Is Indispensable for Maintaining Mitochondrial Homeostasis in Uromodulin-Associated CKD
SA-PO632
"Results
MANF is induced in the TALs carrying the Umod deletion mutation. Genetic ablation of MANF in the mutant TALs suppresses phosphorylation of AMP-activated protein kinase (AMPK) and downstream expression of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) and forkhead box O3 (FOXO3) in isolated primary TAL cells, resulting in impaired mitochondrial biogenesis/oxidative phosphorylation and mitophagy, respectively. The in vitroresults are in line with the in vivo findings. Consequently, MANF deficiency in TALs activates mitochondrial DNA leak-induced STING (stimulator of interferon genes) signaling and hyperinflammation, leading to accelerated renal fibrosis and kidney dysfunction in ADTKD.
Conclusion
For the first time, we discover that MANF is required to maintain mitochondrial homeostasis and acts as a critical molecular linker between ER and mitochondria homeostasis in ADTKD. The key role of MANF in mediating ER-mitochondria crosstalk may also have important implications in other protein misfolding diseases, such as Alzheimer."
https://www.asn-online.org/education/kidneywe...Id=4126122
And recent speech at American Society of Nephrology's annual Kidney Week Conference
"Mesencephalic Astrocyte-Derived Neurotrophic Factor for Treatment of Protein Misfolding Diseases: ADTKD"
https://www.asn-online.org/education/kidneywe...sId=479783
Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Is Indispensable for Maintaining Mitochondrial Homeostasis in Uromodulin-Associated CKD
SA-PO632
"Results
MANF is induced in the TALs carrying the Umod deletion mutation. Genetic ablation of MANF in the mutant TALs suppresses phosphorylation of AMP-activated protein kinase (AMPK) and downstream expression of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) and forkhead box O3 (FOXO3) in isolated primary TAL cells, resulting in impaired mitochondrial biogenesis/oxidative phosphorylation and mitophagy, respectively. The in vitroresults are in line with the in vivo findings. Consequently, MANF deficiency in TALs activates mitochondrial DNA leak-induced STING (stimulator of interferon genes) signaling and hyperinflammation, leading to accelerated renal fibrosis and kidney dysfunction in ADTKD.
Conclusion
For the first time, we discover that MANF is required to maintain mitochondrial homeostasis and acts as a critical molecular linker between ER and mitochondria homeostasis in ADTKD. The key role of MANF in mediating ER-mitochondria crosstalk may also have important implications in other protein misfolding diseases, such as Alzheimer."
https://www.asn-online.org/education/kidneywe...Id=4126122
And recent speech at American Society of Nephrology's annual Kidney Week Conference
"Mesencephalic Astrocyte-Derived Neurotrophic Factor for Treatment of Protein Misfolding Diseases: ADTKD"
https://www.asn-online.org/education/kidneywe...sId=479783
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