Colostral proline-rich polypeptides--immunoregulatory properties and prospects of therapeutic use in Alzheimer's disease.
A proline-rich polypeptide complex (PRP), subsequently called Colostrinin(CLN), was first isolated from ovine colostrum, was shown to possess immunoregulatory properties, including effects on the maturation and differentiation of murine thymocytes and humoral and cellular immune responses, both in vivo and in vitro. PRP seems to restore balance in cellular immune functions and is not species specific. PRP is a complex of peptides of molecular masses ranging from 500 to 3000 Da. The polypeptide contains 25% proline and 40% hydrophobic amino acids. PRP shows a regulatory activity in cytokine (IFN, TNF-alpha, IL-6, IL-10) induction and possesses the ability to inhibit the overproduction of oxygen reactive species and nitric oxide. Besides its immunoregulatory activity, PRP also showed psychotropic properties, improving cognitive activity and behavior of old rats, humans, and chickens. The properties of PRP prompted the authors to propose the complex for the treatment neurodegenerative disorders. Beneficial effects of PRP/Colostrinin were shown for the first time in double-blind placebo-controlled trials and long-term open-label studies. The results were confirmed in multicenter clinical trials. A very important property of PRP/Colostrinin is the prevention of Abeta aggregation and the disruption of already existing aggregates. The same properties were expressed by one of PRP's components, a nonapeptide (NP). Moreover, PRP modulates neurite outgrowth, suppresses uncontrolled activation of cells, reduces 4-HNE-mediated cellular damage, and modulates expression in cellular redox regulation, cell proliferation, and differentiation. Its biological response modifying activity can play an important role in its use in the treatment of Alzheimer's disease.
Janusz
M
M
Department of Immunochemistry, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 R. Weigla, 53-114 Wrocław, Poland. janusz@iitd.pan.wroc.pl
Zabłocka
A
A
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D018697:Nootropic Agents / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
D016229:Amyloid beta-Peptides; D036341:Intercellular Signaling Peptides and Proteins; D018697:Nootropic Agents; D010455:Peptides; C105874:colostrinine