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Brain-site-specific proteome changes induced by neuronal P60TRP expression.

Arulmani Manavalan1, Manisha Mishra, Siu Kwan Sze

  • 1School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.

Neuro-Signals
|February 9, 2013
PubMed
Summary

p60 transcription regulator protein (p60TRP) overexpression in neurons impacts brain proteome, affecting cognitive and neuroprotective functions. This finding offers insights into potential Alzheimer's disease therapeutic strategies.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Proteomics

Background:

  • p60 transcription regulator protein (p60TRP) regulates amyloid precursor protein processing via the non-amyloidogenic pathway by inhibiting beta-secretase.
  • p60TRP is downregulated in Alzheimer's disease brains and influences G-protein-coupled receptor signaling.
  • Understanding the long-term effects of p60TRP in the central nervous system is crucial for neurodegenerative disease research.

Purpose of the Study:

  • To investigate the brain-region-specific proteome profile in transgenic mice with neuronal p60TRP overexpression.
  • To elucidate molecular events associated with long-term p60TRP effects on brain proteome.
  • To explore the implications of p60TRP overexpression for neuronal functions and cognitive capacities.

Main Methods:

  • Proteomics approach utilizing isobaric tags for relative and absolute quantitation (iTRAQ).
  • Analysis of brain-region-specific proteome profiles in transgenic p60TRP mice.
  • Quantification and statistical analysis of protein alterations in the cortex and hippocampus.

Main Results:

  • Identified 2,025 proteins, with 1,735 quantified.
  • Found 56 proteins significantly altered in the cortex and/or hippocampus of transgenic mice.
  • Demonstrated that in vivo neuronal p60TRP overexpression significantly impacts cognitive and neuroprotective capacities.

Conclusions:

  • Neuronal p60TRP overexpression leads to significant alterations in the brain proteome.
  • These proteomic changes are associated with notable effects on cognitive and neuroprotective functions.
  • The study provides insights into the molecular mechanisms underlying p60TRP's role in neuronal health and disease.