Therapeutic approaches against common structural features of toxic oligomers shared by multiple amyloidogenic proteins

Biochem Pharmacol. 2014 Apr 15;88(4):468-78. doi: 10.1016/j.bcp.2013.12.023. Epub 2014 Jan 7.

Abstract

Impaired proteostasis is one of the main features of all amyloid diseases, which are associated with the formation of insoluble aggregates from amyloidogenic proteins. The aggregation process can be caused by overproduction or poor clearance of these proteins. However, numerous reports suggest that amyloid oligomers are the most toxic species, rather than insoluble fibrillar material, in Alzheimer's, Parkinson's, and Prion diseases, among others. Although the exact protein that aggregates varies between amyloid disorders, they all share common structural features that can be used as therapeutic targets. In this review, we focus on therapeutic approaches against shared features of toxic oligomeric structures and future directions.

Keywords: Amyloid oligomers; Anle138b (http://www.cipsm.de/en/publications/researchAreaA/2013/Anle138b_a_novel_oligomer_modulator_for_disease-modifying_therapy_of_neurodegenerative_diseases_such_as_prion_and_Parkinson_s_disease/index.html?style=1); Anti-amyloid small molecules; Baicalein (PubChem CID: 5281605); CLR01 (http://www.med-chemist.com/2012/11/clr01-effectively-inhibits.html); Curcumin (PubChem CID: 969516); Epigallocatechingallate (PubChem CID: 65064); Immunotherapy; Methylene blue (PubChem CID: 6099); Oleuropein (PubChem CID: 5281544); Phenol Red (PubChem CID: 4766); Resveratrol (PubChem CID: 445154); Silibinin (PubChem CID: 31553).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amyloidogenic Proteins / chemistry*
  • Amyloidogenic Proteins / toxicity
  • Animals
  • Biopolymers / chemistry*
  • Biopolymers / toxicity
  • Immunotherapy
  • Mice

Substances

  • Amyloidogenic Proteins
  • Biopolymers