Protective effects of melatonin on mitochondrial biogenesis and mitochondrial structure and function in the HEK293-APPswe cell model of Alzheimer's disease.

ABSTRACT

OBJECTIVE: The effects and mechanisms of melatonin on Alzheimer's disease (AD) are still not researched thoroughly. 20E2 cells (HEK293-APPswe cells) are a cellular model of AD. The modulation effects of melatonin on the structure and function of mitochondria in 20E2 cells need to be studied. MATERIALS AND METHODS: The Alzheimer's disease (AD) cell model was assessed for cell viability, expression levels of mitochondrial biogenesis factors (peroxisome proliferator-activated receptor gamma coactivator 1-alpha [PGC-1α], nuclear respiratory factor 1 [NRF1], nuclear respiratory factor 2 [NRF2], mitochondrial transcription factor A [TFAM]), mitochondrial membrane potential, Na+-K+-adenosine triphosphatase (ATPase) and cytochrome C oxidase activity, adenosine triphosphate (ATP) level, mitochondrial DNA/nuclear DNA (mtDNA/nDNA) ratio, and mitochondrial structure with and without melatonin. RESULTS: Melatonin improved 20E2 cell viability, expression of mitochondrial biogenesis factors (PGC-1α, NRF1, NRF2, TFAM), mitochondrial membrane potential, Na+-K+-ATPase, and cytochrome C oxidase activity, ATP level, mtDNA/nDNA ratio, mitochondrial structure, and decreased amyloidogenic amyloid precursor protein processing. CONCLUSIONS: Mitochondrial biogenesis disorder is associated with the pathogenesis of AD through PGC-1α-NRF-TFAM pathway, and melatonin improves the mitochondrial structure and function by enhancing mitochondrial biogenesis and decreasing amyloidogenic APP processing in Alzheimer's disease.