Given the hierarchical order from mitochondrial qu
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the eventual activation of proinflammatory cytokines in our deletion mutation mice, we envision that treatment with the upstream p-AMPK enhancer MANF, which can restore homeostasis of dysfunctional mitochondria, might be more effective in ADTKD-UMOD. MANF is an 18kD protein and recombinant MANF is readily available. In the future, we will continue to test the therapeutic application of MANF as a novel strategy for the treatment of ADTKD patients caused by various gene mutations. In addition, whether MANF can treat other proteinopathies
resulting from mutant protein aggregates and altered proteostasis, such as Alzheimer’s disease amyotrophic lateral sclerosis and retinitis pigmentosa , is of great interest for the future investigation.