Targeting the autophagy-lysosomal pathway in Huntington disease: a pharmacological perspective

Junsheng Yang; Chaoyue Zhang

doi:10.3389/fnagi.2023.1175598

Targeting the autophagy-lysosomal pathway in Huntington disease: a pharmacological perspective

Front Aging Neurosci. 2023 May 25:15:1175598. doi: 10.3389/fnagi.2023.1175598. eCollection 2023.

Authors

Junsheng Yang¹, Chaoyue Zhang¹

Affiliation

¹ Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, China.

Abstract

The autophagy-lysosomal pathway (ALP) is the major biological pathway responsible for clearing intracellular protein aggregates, therefore a promising target for treating diseases featuring the accumulation of aggregation-prone proteins, such as Huntington disease (HD). However, accumulating evidence indicated that targeting ALP to treat HD is pharmacologically challenging due to the complexity of autophagy and the autophagy defects in HD cells. Here in this mini-review, we summarized the current challenges in targeting ALP in HD and discussed a number of latest findings on aggrephagy and targeted protein degradation, which we believe will provide potential new targets and new strategies for treating HD via ALP.

Keywords: Huntington disease; aggrephagy; autophagy-lysosomal pathway; mHTT; targeted protein degradation.

Publication types

Review

Grants and funding

This work was supported by the National Natural Science Foundation of China (82071432).