Physiological role of NACP,the precursor of non-Abeta component of Alzheimer's disease amyloid

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We found an unrecognized component of Alzheimer's disease (AD) amyloid, named NAC (non-Abeta component of AD amyloid) and cloned cDNA encoding NAC precursor protein, NACP.NACP is turned out to be human homologue of Torpedo synuclein, thus also called alpha-synuclein, later. NACP is a presynaptic protein, and constitutes a gene family with PNP14, or beta-synuclein. It should be particularly noted that expression pattern-for NACP mirrors the distribution of typical AD pathology. We showed that NACP is aberrantly expressed not only in synaptic region, but also in dystrophic neurites in AD brain. Thus, understanding the physiological role of NACP is crucial to clarify the pathophysiological events in AD brain.We utilized an established neuronal cell line, PC12 for this study, and identified a NACP family protein, beta-synuclein with RT-PCR.We have raised specific antibodies against beta-synuclein. Meanwhile, we have found NACP-positive abnormal structures in hippocampus of ischemia brain where neuronal death is observed. This finding suggests that alteration of NACP might be involved in a similar manner in several neurodegenerative diseases, as well as AD.