Targeting Protein Aggregates with Natural Products: An Optional Strategy for Neurodegenerative Diseases

Int J Mol Sci. 2023 Jul 10;24(14):11275. doi: 10.3390/ijms241411275.

Abstract

Protein aggregation is one of the hallmarks of aging and aging-related diseases, especially for the neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS), and others. In these diseases, many pathogenic proteins, such as amyloid-β, tau, α-Syn, Htt, and FUS, form aggregates that disrupt the normal physiological function of cells and lead to associated neuronal lesions. Protein aggregates in NDs are widely recognized as one of the important targets for the treatment of these diseases. Natural products, with their diverse biological activities and rich medical history, represent a great treasure trove for the development of therapeutic strategies to combat disease. A number of in vitro and in vivo studies have shown that natural products, by virtue of their complex molecular scaffolds that specifically bind to pathogenic proteins and their aggregates, can inhibit the formation of aggregates, disrupt the structure of aggregates and destabilize them, thereby alleviating conditions associated with NDs. Here, we systematically reviewed studies using natural products to improve disease-related symptoms by reducing or inhibiting the formation of five pathogenic protein aggregates associated with NDs. This information should provide valuable insights into new directions and ideas for the treatment of neurodegenerative diseases.

Keywords: Aβ; FUS; Htt; natural products; neurodegenerative diseases; protein aggregation; tau; α-Syn.

Publication types

  • Systematic Review
  • Review

MeSH terms

  • Alzheimer Disease*
  • Biological Products* / pharmacology
  • Biological Products* / therapeutic use
  • Humans
  • Neurodegenerative Diseases* / metabolism
  • Parkinson Disease*
  • Protein Aggregates

Substances

  • Protein Aggregates
  • Biological Products