State v. Dewitt Appellant\u27s Reply Brief Dckt. 38556

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Proline-rich polypeptides in Alzheimer's disease and neurodegenerative disorders - Therapeutic potential or a mirage?

The development of effective and safe drugs for a growing Alzheimer disease population is an increasing need at present. Both experimental and clinical evidence support a beneficial effect of proline-rich polypeptides in a number of neurodegenerative diseases, including Alzheimer disease. Experimental data have shown that proline-rich polypeptides isolated from bovine neurohypophisis possess neuroprotective and neuromodulatory properties in mice with aluminum neurotoxicosis or neuronal damage caused by venoms and toxins. Proline-rich polypeptides from ovine colostrums, so called Colostrinin, have been shown to produce cognitive improvement in an experimental model and in patients with Alzheimer disease. However, the precise mechanism underlying the neuroprotective action of proline-rich polypeptides is not very well established. Moreover, studies pointing at a neuroprotective effect of proline-rich polypeptides from bovine neurohypophisis in humans have not been reported thus far. The authors conclude that more detailed information on the mode of action of proline-rich polypeptides is needed as well as confirmation of their efficacy in broad clinical trials before this approach can really show its potential in the treatment of neurodegenerative disorders. (c) 2007 Elsevier Inc. All rights reserved

Neuroprotective action of proline-rich polypeptide-1 in β-amyloid induced neurodegeneration in rats

Original article can be found at: http://www.sciencedirect.com/ Copyright Elsevier [Full text of this article is not available in the UHRA]It is recognized that the main trigger of Alzheimer disease related neurodegeneration is β-amyloid peptide, which subsequently generates different metabolic disorders in neuron and finally leads to neuronal death. Several biologically active products were tested as neuroprotectors, but only few of them demonstrated any efficiency.Proline-rich polypeptide-1 was tested as a neuroprotective agent on Aβ25-35 animal model of Alzheimer disease. Biochemical analysis (determination of spectrum of neuroactive amino acids, such as glutamate, gamma-aminobutyric acid, glycine, aspartate and taurine), as well as behavioral, electrophysiological and morphological studies were performed to reveal the neuroprotective potential of proline-rich polypeptide in rats.Based on the results of our study it can be concluded that proline-rich polypeptide-1 has a potential to be one of the effective preventive or therapeutic agents against neurodegenerative disorders, such as Alzheimer disease.Peer reviewe