colostrinin

[jw]

J Nutr Health Aging. 2009 Mar;13(3):235-41.
New insights into clinical trial for Colostrinin in Alzheimer's
disease.
Szaniszlo P, German P, Hajas G, Saenz DN, Kruzel M, Boldogh I.
Department of Microbiology and Immunology, University of Texas Medical
Branch at Galveston, Galveston, Texas 77555, USA.
BACKGROUND: The pathomechanism of Alzheimer's disease (AD) is
multifactorial although the most popular hypotheses are centered on
the effects of the misfolded, aggregated protein, amyloid beta (Abeta)
and on Tau hyperphosphorylation. OBJECTIVES: Double blinded clinical
trials were planned to demonstrate the effect of Colostrinin (CLN) on
instrumental daily activities of AD patients. The potential molecular
mechanisms by which CLN mediates its effects were investigated by gene
expression profiling. METHODS: RNAs isolated from CLN-treated cells
were analyzed by high-density oligonucleotide arrays. Network and
pathway analyses were performed using the Ingenuity Pathway Analysis
software. RESULTS: The Full Sample Analysis at week 15 showed a
stabilizing effect of CLN on cognitive function in ADAS-cog (p = 0.02)
and on daily function in IADL (p = 0.02). The overall patient response
was also in favor of CLN (p = 0.03). Patients graded as mild on entry
also showed a superior response of ADAS-cog compared to more advanced
cases (p = 0.01). Data derived from microarray network analysis show
that CLN elicits highly complex and multiphasic changes in the cells'
transcriptome. Importantly, transcriptomal analysis showed that CLN
alters gene expression of molecular networks implicated in Abeta
precursor protein synthesis, Tau phosphorylation and increased levels
of enzymes that proteolitically eliminate Abeta. In addition, CLN
enhanced the defense against oxidative stress and decreased expression
of inflammatory chemokines and cytokines, thereby attenuating
inflammatory processes that precede Alzheimer's and other neurological
diseases. CONCLUSION: Together these data suggest that CLN has
promising potential for clinical use in prevention and therapy of
Alzheimer's and other age-associated central nervous system diseases.
PMID: 19262960 [PubMed - indexed for MEDLINE]

Curr Alzheimer Res. 2009 Nov 26. [Epub ahead of print]
Colostral Proline-Rich Polypeptides - Immunoregulatory Properties and
Prospects of Therapeutic Use in Alzheimer's Disease.
Janusz M, Zabłocka A.
Department of Immunochemistry, Institute of Immunology and
Experimental Therapy, Polish Academy of Sciences, 12 R.Weigla, 53-114
Wrocław, Poland. jan...@iitd.pan.wroc.pl.
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.
PMID: 19939229 [PubMed - as supplied by publisher]

J Alzheimers Dis. 2008 Apr;13(3):303-21.
Colostrinin: an oxidative stress modulator for prevention and
treatment of age-related disorders.
Boldogh I, Kruzel ML.
Department of Microbiology and Immunology, University of Texas Medical
Branch at Galveston, TX 77555, USA.
Colostrum-derived proline-rich polypeptide, also known as Colostrinin
(CLN), has been shown to have a stabilizing effect on cognitive
function in Alzheimer's disease patients. This complex action of CLN
could be related to prevention of amyloid-beta peptide aggregation, as
shown in in vitro studies, and its impact on delicate cassettes of
signaling pathways common to cellular redox regulation, proliferation
and differentiation. Studies on cultured cells showed that CLN
modulates intracellular levels of reactive oxygen species (ROS), via
regulation of glutathione metabolism, activity of antioxidant enzymes
and mitochondria function. Due to an improvement in senescence-
associated mitochondrial dysfunction and a decrease in ROS generation,
CLN decelerates the aging processes of both cultured cells and
experimental animals. When given orally to mice, CLN increased the
lifespan and improved various motor and sensory activities. Although
the molecular basis by which CLN exerts its diverse effects are still
under investigation, the regulatory effect on the cellular redox state
via maintenance of mitochondrial function and modification of ROS-
induced cell signaling seem to be of great importance. In this
article, we examine experimental data pertinent to the mechanism of
action, including a review of CLN's utility in the maintenance of
physiological processes in which oxidative stress has an etiological
role.
PMID: 18430998 [PubMed - indexed for MEDLINE]