Review article Proline-rich polypeptides in Alzheimer's disease and neurodegenerative disorders — Therapeutic potential or a mirage? A. Gladkevich a, ⁎ , F. Bosker a , J. Korf a , K. Yenkoyan b , H. Vahradyan b , M. Aghajanov b a Department of Psychiatry, University Medical Centre Groningen, University Groningen, the Netherlands b Institute of Biochemistry, Yerevan State Medical University, Yerevan, Armenia Received 3 April 2007; received in revised form 4 May 2007; accepted 12 June 2007 Available online 21 June 2007 Abstract 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. © 2007 Elsevier Inc. All rights reserved. Keywords: Alzheimer's disease; Colostrinin; Neurodegenerative disorders; Proline-rich-polypeptides Contents 1. Introduction ............................................................. 1348 2. Biochemistry of PRPs ........................................................ 1349 2.1. Colostral PRP ......................................................... 1349 2.2. Hypothalamic and hypophyseal PRPs ............................................ 1350 2.3. Localisation of PRPs ..................................................... 1350 3. Biological properties of hypothalamic and colostral PRPs ...................................... 1350 3.1. PRP-1 and growth factors (in vitro) ............................................. 1350 3.2. PRP-1 and caspase activity .................................................. 1350 3.3. PRP-1 and crush syndrome .................................................. 1351 3.4. PRP-1 against cobra venom and trauma-induced neuronal injure (in vivo) ......................... 1351 3.5. PRP-1 and aluminium neurotoxicosis (in vivo) ....................................... 1351 Progress in Neuro-Psychopharmacology & Biological Psychiatry 31 (2007) 1347 – 1355 www.elsevier.com/locate/pnpbp Abbreviations: AD, Alzheimer's disease; ADAS-cog, Alzheimer's Disease Assessment Scale—cognitive portion; CLN, colostrinin; GFAP, glial fibrillary acidic protein; IADL, Instrumental Activities of daily Living; MRTP, 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine; PBL, peripheral blood leukocytes; PRPs, proline-rich polypeptides; NVAG, neurophysin–vasopressin-associated glycoprotein; NSO, nucleus supraopticus; NPV, nucleus paraventricularis; NP, nonapeptide fragment; NGF, nervous growth factor; MMSE, Mini-Mental State Examination. ⁎ Corresponding author. Department of Psychiatry, University Medical Centre Groningen, Hanzeplein 1, P.O. Box 30.001, 9700 RB Groningen, the Netherlands. Tel.: +31 50 361 2109; fax: +31 50 361 9132. E-mail address: a.v.gladkevich@psy.umcg.nl (A. Gladkevich). 0278-5846/$ - see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2007.06.005