title: Alpha-crystallin-derived peptides as therapeutic chaperones.
abstract: BACKGROUND
  The demonstration of chaperone-like activity in peptides (mini-chaperones) derived from α-crystallin's chaperone region has generated significant interest in exploring the therapeutic potential of peptide chaperones in diseases of protein aggregation. Recent studies in experimental animals show that mini-chaperones could reach intended targets and alter the disease phenotype. Although mini-chaperones show potential benefits against protein aggregation diseases, they do tend to form aggregates on storage. There is thus a need to fine-tune peptide chaperones to increase their solubility, pharmacokinetics, and biological efficacy.
  
  
  METHODS
  This review summarizes the properties and the potential therapeutic roles of mini-chaperones in protein aggregation diseases and highlights some of the refinements needed to increase the stability and biological efficacy of mini-chaperones while maintaining or enhancing their chaperone-like activity against precipitation of unfolding proteins.
  
  
  CONCLUSIONS
  Mini-chaperones suppress the aggregation of proteins, block amyloid fibril formation, stabilize mutant proteins, sequester metal ions, and exhibit antiapoptotic properties. Much work must be done to fine-tune mini-chaperones and increase their stability and biological efficacy. Peptide chaperones could have a great therapeutic value in diseases associated with protein aggregation and apoptosis.
  
  
  CONCLUSIONS
  Accumulation of misfolded proteins is a primary cause for many age-related diseases, including cataract, macular degeneration, and various neurological diseases. Stabilization of native proteins is a logical therapeutic approach for such diseases. Mini-chaperones, with their inherent antiaggregation and antiapoptotic properties, may represent an effective therapeutic molecule to prevent the cascade of protein conformational disorders. Future studies will further uncover the therapeutic potential of mini-chaperones. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease.
authors.affiliation: Department of Ophthalmology, University of Missouri School of Medicine, Columbia, MO 65212, USA.
authors.forename: Murugesan
authors.initials: M
authors.lastname: Raju
authors.affiliation: Department of Ophthalmology, University of Missouri School of Medicine, Columbia, MO 65212, USA.
authors.forename: Puttur
authors.initials: P
authors.lastname: Santhoshkumar
authors.affiliation: Department of Ophthalmology, University of Missouri School of Medicine, Columbia, MO 65212, USA; Department of Biochemistry, University of Missouri School of Medicine, Columbia, MO 65212, USA. Electronic address: sharmak@health.missouri.edu.
authors.forename: K
authors.initials: K
authors.lastname: Krishna Sharma
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D005901:Glaucoma / Q000188:drug therapy* / Q000473:pathology; D018832:Molecular Chaperones / Q000627:therapeutic use; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use*; D066263:Protein Aggregation, Pathological / Q000188:drug therapy*; D012164:Retinal Diseases / Q000188:drug therapy* / Q000473:pathology; D038201:alpha-Crystallins / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D018832:Molecular Chaperones; D010455:Peptides; D038201:alpha-Crystallins
keywords: Crystallins; Mini-chaperones; Peptide; Protein aggregation; Therapeutics