Fig. 2

Potential neuroprotective effects mediated by time-restricted eating in Huntington’s disease (HD). a Chronic caloric exposure increases levels of insulin and IGF-1 and decreases the cellular AMP/ATP ratio, leading to activation of mTOR and downregulation of AMPK activity, respectively. As a result, autophagic processes are not stimulated and mHTT protein aggregates accumulate, which further inhibit cellular autophagic activity. Decreased SIRT1 in a fed state and decreased BDNF expression seen in HD pathology result in downregulation of PGC-1α and subsequent oxidative stress, neurodegeneration, and metabolic dysregulation. b Fasting in TRE downregulates mTOR and upregulates AMPK, which stimulate autophagy through ULK1 activation. Increased autophagy is known to reduce mHTT aggregate formation in neurons. Fasting in TRE also upregulates SIRT1, which has been shown to potentiate PGC-1α and promote oxidative stress resistance and mitochondrial biogenesis. States of fasting additionally result in increased peripheral blood levels of BHB which upregulate BDNF expression. BDNF induces neurogenesis and synaptic plasticity and activates PGC-1α for further metabolic regulation and antioxidant effects. Created with BioRender.com