Targeting protein aggregation for the treatment of degenerative diseases

Nat Rev Drug Discov. 2015 Nov;14(11):759-80. doi: 10.1038/nrd4593. Epub 2015 Sep 4.


The aggregation of specific proteins is hypothesized to underlie several degenerative diseases, which are collectively known as amyloid disorders. However, the mechanistic connection between the process of protein aggregation and tissue degeneration is not yet fully understood. Here, we review current and emerging strategies to ameliorate aggregation-associated degenerative disorders, with a focus on disease-modifying strategies that prevent the formation of and/or eliminate protein aggregates. Persuasive pharmacological and genetic evidence now supports protein aggregation as the cause of postmitotic tissue dysfunction or loss. However, a more detailed understanding of the factors that trigger and sustain aggregate formation and of the structure-activity relationships underlying proteotoxicity is needed to develop future disease-modifying therapies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Factors / pharmacology
  • Biological Factors / therapeutic use
  • Humans
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology
  • Prealbumin / antagonists & inhibitors
  • Prealbumin / chemistry
  • Prealbumin / metabolism
  • Protein Aggregation, Pathological / drug therapy*
  • Protein Aggregation, Pathological / metabolism
  • Protein Aggregation, Pathological / pathology
  • Protein Folding / drug effects
  • Protein Transport / drug effects*
  • Structure-Activity Relationship
  • Treatment Outcome


  • Biological Factors
  • Prealbumin