Colostral Proline-Rich Polypeptides – Immunoregulatory Properties and Prospects of Therapeutic Use in Alzheimers Disease

Abstract

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.

Can proline‐rich polypeptide complex mimic the effect of nerve growth factor?

“…The RevertAid TM First Strand cDNA Synthesis Kit was from Fermentas (Life Sciences). 1H- [1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (ODQ) and 1-methyl-3-isobutylxanthine (IBMX) were from Cayman Chemical (San Diego, CA). Monoclonal antibody: anti-nNOS, anti-ERK1/2, and anti-phospho-ERK1/ 2, and U0126-selective MEK 1/2 inhibitor were from Cell Signaling (Boston, MA).…”

“…Immunologically active PRPs were identified in the hypothalamus and in biological fluids such as colostrum and milk. PRPs produced by bovine hypothalamic magnocellular cells act as neuroprotectors or function as putative neurotransmitters and immunomodulators and were identified in various brain structures of intact and trauma-injured rats [1]. Colostrum and milk-the first mammalian nourishment-are the richest reservoir of constituents of great importance in newborn development.…”

“…Another possibility to explain the therapeutic effect of PRP/Colostrinin is its effect on neurite outgrowth. Also, Colostrinin, as well as its constituent nonapeptide not only inhibits aggregation of amyloid b and formation of fibrillar structures but also can dissolve aggregates already formed, acting as a b-sheet breaker [1,2]. Nerve growth factor (NGF) is a neurotrophin that has been shown to exert a number of different, distinguishable effects on neurons, such as survival, growth of fibers, and differentiation of target neurons [3][4][5][6].…”

Medicinal Plants Anti-cholinesterase Activity and the Potential for Alzheimer’s Disease Treatment

“…This is an anti-amyloid approach where many parts of amyloid precursor protein (APP) metabolism are targeted [36]. APP processing can also be targeted by the inhibition of β-secretase [37], GRL-8234 is an example of β-secretase that proves promising in preclinical investigations [38].…”

“…Sponsored studies in 2001 using Aβ42 in QS21 [36], suggest treatment with Aβ42 peptide produced antibodies against Aβ, leading to reduced cerebrospinal tau levels and hence less cognitive decline [45] …”