COMPARISONS OF THE NACP SELF-OLIGOMERIZATIONS INDUCED BY A-BETA-25-35IN THE PRESENCE OF DICYCLOHEXYLCARBODIIMIDE AND N-(ETHOXYCARBONYL)-2-ETHOXY-1,2-DIHYDROQUINOLINE

NACP, the precursor protein of the non-amyloid beta/A4 protein (A beta ) component of Alzheimer's disease (AD) amyloid, also known as alpha-s ynuclein was shown to undergo self-oligomerization only in the presenc e of a modified A beta fragment (residues 25-35) by using a relatively hydrophobic coupling reagent, dicyclohexylcarbodiimide (DCCD). Since the oligomerization not only required a relatively high concentration of DCCD but also its efficiency was suppressed even at a slightly basi c pH of 7.5, another coupling reagent called N-(ethoxycarbonyl)-2-etho xy-1,2-dihydroquinoline (EEDQ) was examined in order to make use of th is technique to access the functional aspects of NACP in vitro by expl oring more accurate and reproducible reaction conditions. The EEDQ als o gave rise to the NACP oligomerization only in the presence of A beta 25-35 among the variously modified A beta peptides. The reagent was a bout three times more effective than DCCD in terms of its optimal conc entration to visualize the oligomers. In addition, its oligomerizing p otency was not affected by the basic condition. Although physiological and pathological significance of the NACP self-oligomerization are cu rrently unknown, this dramatic phenomenon and its visualization techni que could shed light on the determination of molecular relationships o f NACP with various intracellular or extracellular biomolecules relate d to the pathological conditions of Alzheimer's and Parkinson's diseas es.