beta-Endorphin inhibits the expression of amyloid precursor protein in SK-N-SH neuroblastoma cells expressing high levels of mutant amyloid precursor protein

Alzheimer's is a neurodegenerative disorder characterized by increased deposition of insoluble extracellular amyloid plaques in the brain with neurofibrillary tangles within the neurons [1,8]. Amyloid plaque formation or amyloidosis results from the deposition of amyloid-beta peptide produced from amyloid precursor protein (APP) by the activity of alpha, beta and gamma-secretases.[8]. APP gene promoter contains a cAMP response element (CRE) and is responsive to changes in intracellular cAMP levels. Agents that cause elevated intracellular cAMP through cell-signaling have been shown to increase the expression of APP mRNA and protein levels[9]. beta-endorphin has been shown to modulate intracellular cAMP through cell signaling[21]. To determine the effect of beta-endorphin on the expression of APP, SK-N-SH Neuroblastoma cells were treated with beta-endorphin and its effect was studied using RNA and protein analyses. Northern blot and RT-PCR analyses indicated decreased levels of transcription of the APP mRNA. Western blot analysis showed a corresponding decrease in the expression of the protein. In some earlier experiments treatment with propranolol showed a similar effect; forskolin on the other hand caused an increase in APP mRNA levels and corresponding increase in APP expression. The elevated physiological release of beta-endorphin may likely have a beneficial effect in Alzheimer's patients.