Alleviation of a polyglucosan storage disorder by enhancement of autophagic glycogen catabolism

ABSTRACT: This work employs Adult Polyglucosan Body Disease (APBD) models to explore the efficacy and mechanism of action of the polyglucosan-reducing compound 144DG11. APBD is a glycogen storage disorder (GSD) caused by glycogen branching enzyme (GBE) deficiency causing accumulation of poorly branched glycogen inclusions called polyglucosans. 144DG11 improved survival and motor parameters in a GBE knockin (Gbeys/ys) APBD mouse model. 144DG11 reduced polyglucosan and glycogen in brain, liver, heart, and peripheral nerve. Indirect calorimetry experiments revealed that 144DG11 increases carbohydrate burn at the expense of fat burn, suggesting metabolic mobilization of pathogenic polyglucosan. At the cellular level, 144DG11 increased glycolytic, mitochondrial, and total ATP production. The molecular ta

SUBMITTER: Dr. Or Kakhlon 

PROVIDER: S-SCDT-EMM-2021-14554 | biostudies-other |

REPOSITORIES: biostudies-other