Are beta-sheet breaker peptides dissolving the therapeutic problem of Alzheimer's disease?
Alzheimer's disease (AD) is a neurodegenerative disorder for which there is no cure or effective treatment. One of the major neuropathological signatures of AD is the deposition of amyloid plaques in the brain of affected people. Although the role of these structures in the pathogenesis of the disease is not fully understood, recent findings have provided evidence that amyloid may be a key player in the disease. Therefore, preventing and reversing cerebral amyloid deposition have become an attractive therapeutic strategy for AD. We have engineered synthetic beta-sheet breaker peptides to bind soluble amyloid peptide and prevent and reverse its conversion to the beta-sheet rich aggregated structure, precursor of the amyloid plaques. Results in vitro, in cell culture and in vivo suggest that beta-sheet breaker peptides might be candidates for an AD-therapy focused to reduce amyloid deposition.
Permanne
B
B
Serono Pharmaceutical Research Institute, Geneva, Switzerland.
Adessi
C
C
Fraga
S
S
Frossard
M J
MJ
Saborio
G P
GP
Soto
C
C
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy*; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000187:drug effects*; D016229:Amyloid beta-Peptides / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D017433:Protein Structure, Secondary / Q000187:drug effects*
D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)