Alzheimer Disease: Boldogh I

Boldogh I, Kruzel ML. · Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, TX 77555, USA. · J Alzheimers Dis. · Pubmed #18430998 No free full text.

Abstract: 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.

Boldogh I, Liebenthal D, Hughes TK, Juelich TL, Georgiades JA, Kruzel ML, Stanton GJ. · Department of Microbiology and Immunology. The University of Texas Medical Branch, Galveston, TX 77555, USA. · J Mol Neurosci. · Pubmed #12794306 No free full text.

Abstract: In previous studies we showed that colostrinin (CLN), a complex of proline-rich polypeptides derived from ovine colostrum, induces mitogenic stimulation, as well as a variety of cytokines in human peripheral blood leukocytes, and possesses antioxidant activity in pheochromocytoma (PC12) cells. In this study we investigated the effects of CLN on 4-hydroxynonenal (4HNE)-mediated adduct formation, generation of reactive oxygen species (ROS), glutathione (GSH) metabolism, and the modification of signal transduction cascade that leads to activation of c-Jun N-terminal kinase (JNK) in PC12 cells. Here we demonstrate that CLN (1) reduced the abundance of 4HNE-protein adducts, as shown by fluorescent microscopy and Western blot analysis; (2) reduced intracellular levels of ROS, as shown by a decrease in 2',7'-dichlorodihydro-fluorescein-mediated fluorescence; (3) inhibited 4HNE-mediated GSH depletion, as determined fluorimetrically; and (4) inhibited 4HNE-induced activation of JNKs. Together, these findings suggest that CLN appears to down-regulate 4HNE-mediated lipid peroxidation and its product-induced signaling that otherwise may lead to pathological changes at the cellular and organ level. These findings also suggest further that CLN could be useful in the treatment of diseases such as Alzheimer's, as well as those in which ROS are implicated in pathogenesis.