These findings indicate that persistent accumulation of DNA damage and subsequent chronic activation of the downstream DNA damage-response ATM and p53 pro-apoptotic signaling pathways may trigger neuronal dysfunction and neuronal death in ALS.
Increasing evidence indicates that DNA damage and p53 activation play major roles in the pathological process of motor neuron death in amyotrophic lateral sclerosis (ALS).
We found that hTERT expression level was significantly lower in ALS patients and was correlated either to p53 mRNA expression or p21 expression, pointing out the hypothesis that telomerase inhibition could be a pathogenetic contributor to neurodegeneration in ALS.
Recently, Eve et al.(2007) reported that the expression of TP53 (NM_000546) was increased by 2.1-fold in whole spinal cord and 2.7-fold in the ventral horn of amyotrophic lateral sclerosis (ALS) patients.
These results indicate that p53 plays a functional role in oxidative stress-induced cell death and supports the possibility that elevated p53 could be involved in motor neuron death in ALS and the wobbler mouse.
These results indicate that p53 plays a functional role in oxidative stress-induced cell death and supports the possibility that elevated p53 could be involved in motor neuron death in ALS and the wobbler mouse.
This article gives an outline of molecular biological approaches to analysis of neurological disorders such as giant cell glioblastoma (GGBM) and amyotrophic lateral sclerosis (ALS), and their respective animal models: p53 knockout mice for GGBM and mutant superoxide dismutase-1 transgenic mice for ALS.
Despite evidence that p53 plays an important role after acute neuronal injury, the current study suggests that p53 is not significantly involved in cell death in the G93A+ transgenic mouse model of familial ALS.