Repurposing small-molecule drugs for modulating toxic protein aggregates in neurodegenerative diseases

Neurodegenerative diseases (NDs) are often age-related disorders that can cause dementia in people, usually over 65 years old, are still lacking effective therapies. Some NDs have recently been linked to toxic protein aggregates, for example Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis and Huntington disease; therefore, mulating toxic protein aggregates would be a promising therapeutic strategy. Moreover, drug repurposing, in other words exploiting drugs that are already in use for another indication, has been attracting mounting attention for potential therapeutic purposes in NDs. Thus, in this review, we focus on summarizing a series of repurposed small-molecule drugs for eliminating or inhibiting toxic protein aggregates and further discuss their intricate molecular mechanisms to improve the current ND treatment. Taken together, these findings will shed new light on exploiting more repurposed small-molecule drugs targeting different types of toxic proteins to fight NDs in the future.

Automated summary

Neurodegenerative diseases are common age-related disorders without effective therapies. Recent studies have found a link between some neurodegenerative diseases and toxic protein aggregates, suggesting that mimicking these aggregates may be a promising therapeutic strategy. Repurposing existing drugs for other indications has also gained attention as a potential treatment approach. This review focuses on summarizing repurposed small-molecule drugs for neurodegenerative diseases and discussing their molecular mechanisms.