Inhibition of beta-amyloid toxicity by short peptides containing N-methyl amino acids.
Single N-methyl amino acid-containing peptides related to the central hydrophobic region beta16-20 (Lys-Leu-Val-Phe-Phe) of the beta-amyloid protein are able to reduce the cytotoxicity of natural beta1-42 in PC12 cell cultures. N-methyl phenylalanine analogs yield statistically significant increments in cell viability (Student's t-test < 0.01%) and are nontoxic in the same assay. These promising results indicate that these peptide molecules could be a starting point for the development of potential therapeutic compounds for the treatment of Alzheimer's disease.
Cruz
M
M
Institut de Recerca Biomèdica de Barcelona, Parc Científic de Barcelona-UB, Josep Samitier 1, 08028 Barcelona, Spain.
Tusell
J M
JM
Grillo-Bosch
D
D
Albericio
F
F
Serratosa
J
J
Rabanal
F
F
Giralt
E
E
D000544:Alzheimer Disease / Q000378:metabolism; D000596:Amino Acids / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D001681:Biological Assay; D002470:Cell Survival; D005562:Formazans / Q000032:analysis; D016716:PC12 Cells; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D013778:Tetrazolium Salts / Q000032:analysis
D000596:Amino Acids; D016229:Amyloid beta-Peptides; D005562:Formazans; D010455:Peptides; D013778:Tetrazolium Salts; C079782:MTT formazan