Increase of glycogen storage by sodium arsenite in rat cortical astrocytes through glycogen synthase activation and its association to toxicity

Pairor, Selapoom; Homkajorn, Benjaporn; Niyomchan, Apichaya; Suntararuks, Sumitra; Watcharasit, Piyajit; Satayavivad, Jutamaad

doi:10.1007/s13530-021-00094-6

Cited by 2 publications

(1 citation statement)

References 40 publications

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“…Our observations are strong enough to suggest that physiological stress is one of the triggers for GS activation, and the glycogen accumulation seen in these conditions could represent one of the readouts of the neuronal stress response mechanism. Indeed, increased levels of glycogen in neuronal cultures exposed to physiological stressors have been reported in the literature ( Wang et al, 2013 ; Saez et al, 2014 ; Gusarov et al, 2017 ; Rai et al, 2018 ; Lytridou et al, 2020 ; Pairor et al, 2021 ). Therefore, overexpression of GS in the HD fly line would have supplemented the endogenous GS-initiated autophagy process, better protecting neurons from cytotoxicity and extending their lifespan.…”

Section: Discussionmentioning

confidence: 90%

Increase in brain glycogen levels ameliorates Huntington's disease phenotype and rescues neurodegeneration in Drosophila

Onkar,

Sheshadri,

Rai

et al. 2023

Disease Models &Amp; Mechanisms

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Under normal physiological conditions, the mammalian brain contains very little glycogen, most of which is stored in astrocytes. However, the aging brain and subareas of the brain in patients with neurodegenerative disorders tend to accumulate glycogen, the cause and significance of which remain largely unexplored. Using cellular models, we have recently demonstrated a neuroprotective role for neuronal glycogen and glycogen synthase in the context of Huntington's disease. To gain insight into the role of brain glycogen in regulating proteotoxicity, we utilized a Drosophila model of Huntington's disease in which glycogen synthase was either knocked down or expressed ectopically. Enhancing glycogen synthesis in the brains of flies with Huntington's disease decreased mutant Huntingtin aggregation and reduced oxidative stress by activating auto-lysosomal functions. Further, the overexpression of glycogen synthase in the brain rescues photoreceptor degeneration, improves locomotor deficits, and increases fitness traits in Huntington's disease model. We thus provide in vivo evidence for the neuroprotective functions of glycogen synthase and glycogen in neurodegenerative conditions and their role in the neuronal autophagy process.

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