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Keywords:

  • astrocytic cells;
  • β-amyloid precursor protein;
  • melatonin;
  • neuroblastoma cells;
  • PC12 cells;
  • pineal gland hormone

Abstract: Melatonin is released in mammals during the dark phase of the circadian cycle, and its production declines with age in animals and humans. Since supplemental administration of melatonin may be beneficial in delaying age-related degenerative conditions, it is necessary to study its effect on neuronal differentiation and the processing of key neuronal proteins, such as β-amyloid precursor protein (βAPP) and synaptophysin. One of the important pathological hallmarks of Alzheimer's disease (AD) is the cerebrovascular deposition of amyloid plaques. The amyloid in senile plaques is mainly composed of the amyloid β-peptide (Aβ) of 39–43 amino acids derived from a larger βAPP. The proteolytic cleavage by ‘χ-secretase’generate soluble derivatives of βAPP (sAPP), lacking the cytoplasmic tail. transmembrane domain, and a small portion of the extracellular domain. Here levels of sAPP and βAPP were analyzed in cell lines of different origins by Western immunoblot of samples from conditioned media and cell lysates, respectively. Normal levels of secretion of sAPP into conditioned media were severely inhibited by treating different cell lines with a high dose of melatonin. In PC12 cells, levels of the fully matured βAPP forms of the post-Golgi compartment were more drastically decreased than the unglycosylated βAPP of the endoplasmic-reticulum (ER) forms. In other cell types, the unglycosylated ER-bound βAPP derivatives are predominant forms that were marginally affected by melatonin treatment. When the treatment of cells with melatonin was withdrawn, the normal level of secretion of sAPP was restored. Melatonin reduces the secretion of soluble Aβ. Melatonin also inhibits the secretion of synaptophysin in PC12 cells. Taken together, these data suggest that melatonin probably affects the secretion of sAPP in the conditioned medium by interfering with its full maturation, and melatonin also affects the presysnaptic terminal marker.