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.
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