Transcription factor p53 in degenerating spinal cords

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• The causes of motor neuron loss in amyotrophic lateral sclerosis (ALS) remain unclear.
• The transcription factor p53 can induce apoptosis, a process implicated in neurodegeneration.
• The wobbler mouse is a model for motor neuron loss, showing deficits and cell death.

Purpose of the Study:

• To investigate the role of the transcription factor p53 in motor neuron cell death.
• To determine if elevated p53 levels are associated with motor neuron disorders like ALS.

Main Methods:

• Compared p53 expression in wobbler mice and normal littermates using microarray, qRT-PCR, and western blotting.
• Analyzed p53 expression in human ALS spinal cords versus age-matched controls via qRT-PCR.
• Utilized pifithrin-alpha, a p53 inhibitor, in organotypic mouse spinal cord slice cultures exposed to oxidative stress (FeSO4).
• Assessed cell viability using the MTT assay.

Main Results:

• Wobbler mice showed increased p53 signal (2.2-fold by microarray, 6.6-fold by qRT-PCR).
• Human ALS spinal cords exhibited a 2.7-fold increase in p53 expression compared to controls.
• p53 inhibition with pifithrin-alpha significantly reduced FeSO4-induced cell death in spinal cord slice cultures.

Conclusions:

• p53 plays a functional role in oxidative stress-induced spinal cord cell death.
• Elevated p53 expression may contribute to motor neuron death in ALS and the wobbler mouse model.