Melatonin ameliorated okadaic-acid induced Alzheimer-like lesions

Acta Pharmacol Sin. 2004 Mar;25(3):276-80.

Abstract

Aim: To explore the protective effects of melatonin (Mel) on the abnormal phosphorylation of neuronal cytoskeletal proteins.

Methods: We generated a neuroblastoma (SH-SY5Y) cell system in which cytoskeletal proteins are abnormally phosphorylated resulting in microtubule disruption due to the marked inhibition of protein phosphatase activities by okadaic acid (OA).

Results: OA-induced declines in cell viability and mitochondrial metabolic activity were remarkably prevented by Mel. In addition, the hyperphosphorylation/accumulation of neurofilament-(NF-) H/M subunits and the disruption of microtubules, induced by OA, were significantly inhibited by Mel.

Conclusion: Our results suggest multiple protective functions of Mel against a series of pathological lesions known to culminate in AD, including abnormal phosphorylation of cytoskeletal proteins, microtubule disassembly and mitochondrion-initiated cell toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / pathology
  • Cell Survival / drug effects
  • Humans
  • Melatonin / pharmacology*
  • Microtubules / drug effects
  • Microtubules / pathology*
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Neuroblastoma / pathology
  • Neurofilament Proteins / metabolism*
  • Neuroprotective Agents / pharmacology*
  • Okadaic Acid / pharmacology*
  • Phosphorylation
  • Tumor Cells, Cultured

Substances

  • Neurofilament Proteins
  • Neuroprotective Agents
  • Okadaic Acid
  • Melatonin