The protective effects of the nutraceutical, colostrinin, against Alzheimer's disease, is mediated via prevention of apoptosis in human neurones induced by aggregated beta-amyloid.
OBJECTIVE
It has previously been demonstrated that oral administration of ovine Colostrinin (CLN), a proline-rich polypeptide isolated from ovine colostrum, can effectively treat Alzheimer's disease patients. This study aims to determine whether CLN has effects on the aggregation and toxicity of synthetic beta-amyloid (Abeta), implicated as a causative agent of AD.


METHODS
Using cell assays, we examined if pre-treatment of neuronal cells with CLN confers protection.


RESULTS
The data from cytotoxicity assays (using MTT and LDH) demonstrated that pre-treatment of human neuronal SHSY-5Y cells with 5 microg/ml CLN, for 24 hours, confers neuroprotection against Abeta-induced neurotoxicity. Twenty-four hour pre-treatment with 5 microg/ml CLN was also shown to reduce Abeta 1-40-induced apoptosis in human neuronal cells as determined via qualitative and quantitative apoptosis assays.


CONCLUSIONS
The neuroprotection conferred with CLN pre-treatment was reduced with the Fas ligand (FasL) binding antibody Nok1, suggesting that the effects of CLN may involve a Fas:soluble FasL interaction. These findings indicate that CLN could possibly play a role in the prevention of AD pathogenesis, though the inhibition of Fas-mediated apoptosis.
Douraghi-Zadeh
D
D
Neurodegeneration Unit, Basic Medical Sciences, St. George's, University of London, Cranmer Terrace, Tooting, London, UK.
Matharu
B
B
Razvi
A
A
Austen
B
B
D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D019587:Dietary Supplements; D053222:Fas Ligand Protein / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009687:Nuclear Proteins / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D012359:tRNA Methyltransferases
D016229:Amyloid beta-Peptides; D053222:Fas Ligand Protein; D036341:Intercellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; D009687:Nuclear Proteins; D010455:Peptides; C105874:colostrinine; C065028:NOP2 protein, human; D012359:tRNA Methyltransferases