The involvement of hippocampal cholinergic neurostimulating peptide and its precursor in Alzheimer pathogenesis

Hippocampal cholinergic neruostimulating peptide (HCNP) induces acethylcholine synthesis in the adult hippocampus of mice via increasing the amount of cholineacethyl transferase. The precursor protein of HCNP (HCNP-pp), composed of 186 amino acids, is a multifunctional protein, such as c-Raf kinase inhibitory protein and phosphatidylethanolamine-binding protein. In the adult hippocampus, HCNP-pp co-localizes in presynapse terminals with non-phosphorylated collapsin response mediator protein (CRMP)-2, and might play a crucial role in hippocampal neuronal activity. The quantitative alteration of HCNP-pp might be related to the phosphorylation of CRMP-2. The expression of HCNP-pp mRNA is decreased in hippocampal pyramidal neurons of CA1 from the early stage in Alzheimer's disease. The HCNP-related antigens are also deposited in the Hirano body, one locus of Alzheimer pathology. CRMP-2 is one of microtubule-associated proteins such as tau protein, and its phosphorylated form increased in the hippocampus of Alzheimer brains. HCNP and HCNP-pp might be candidates for the key molecules as a therapeutic target in Alzheimer's disease.