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Differentiation of the SH-SY5Y Human Neuroblastoma Cell Line
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Methamphetamine regulates βAPP processing in human neuroblastoma cells.

Mayuri Shukla1, Subhamita Maitra2, Jean-François Hernandez3

  • 1Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, 73170, Thailand; The Research Center for Neuroscience, Mahidol University, Nakhon Pathom, 73170, Thailand; Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok, 10210, Thailand.

Neuroscience Letters
|February 17, 2019
PubMed
Summary

Methamphetamine alters amyloid precursor protein (APP) processing in brain cells. High doses may worsen cognitive decline, while short-term use might offer cognitive benefits in Alzheimer's disease (AD).

Keywords:
Alzheimer’s diseaseDrug abuseMetabolismMethamphetamineSecretaseβAPP

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Cell Biology

Background:

  • Methamphetamine (Meth) abuse is a global health issue causing neurotoxicity and cognitive disorders.
  • Meth exposure may increase the risk of premature Alzheimer's disease (AD), characterized by amyloid plaques.
  • Previous research shows mixed effects of Meth on cognition, depending on dosage and duration.

Purpose of the Study:

  • To investigate the impact of Methamphetamine on beta-amyloid precursor protein (βAPP) metabolism.
  • To examine Methamphetamine's effects on βAPP-cleaving secretases (BACE1 and ADAM10) in a human neuroblastoma cell line.

Main Methods:

  • Utilized the human neuroblastoma SH-SY5Y cell line.
  • Assessed the expression and catalytic activity of BACE1 and ADAM10 following Methamphetamine exposure.
  • Analyzed the cleavage of βAPP under different Methamphetamine treatment conditions.

Main Results:

  • Methamphetamine dose-dependently increased the expression and activity of BACE1, a key enzyme in amyloid-beta production.
  • Methamphetamine's effect on α-secretase (ADAM10) activity and βAPP α-cleavage showed a bell-curve response.
  • This study is the first to show Methamphetamine's control over βAPP-cleaving secretases.

Conclusions:

  • Methamphetamine significantly influences βAPP metabolism by modulating secretase activity.
  • High-dose Methamphetamine may contribute to cognitive decline, potentially through increased BACE1 activity.
  • Acute, short-term Methamphetamine use might enhance cognition by stimulating sAPPα, potentially benefiting conditions like AD.