Age- and disease-related autophagy impairment in Huntington disease: New insights from direct neuronal reprogramming

Autophagy impairment in Huntington disease (HD) has been reported for almost two decades. However, the molecular mechanisms underlying this phenomenon are still unclear. This is partially because it is challenging to model the impact of the disease-causing mutation, aging, as well as the selective vulnerability of neurons in a single model. Recently developed direct neuronal reprogramming that allows researchers to induce neurons-of-interest retaining biological aging information made it possible to establish HD cellular models to study more relevant age- and disease-related molecular changes in neurons. We here summarized the findings from a few latest studies utilizing directly reprogrammed HD neurons and discussed the new insights they brought to the understanding of the age- and disease-related autophagy impairment in HD.