INTRODUCTION In this review we will study the role of protein p53 in neurodegenerative processes and conduct a detailed analysis of the mechanisms responsible for regulating its levels and biological activity. We analyse the neuropathologies in which this protein is involved, such as Alzheimer’s and Parkinson’s diseases and amyotrophic lateral sclerosis, and we will also examine its regulation by second messengers such as the reactive species of oxygen and calcium, showing the signalling paths involved in the apoptotic processes. DEVELOPMENT. The year 2004 sees the 25th anniversary of the discovery of protein p53. At first p53 was wrongly attributed with an oncogenic function due to its capacity to bind to the T antigen of the virus SV40 in transformed cells. Nevertheless, it was not until 1989 that it was attributed with its true physiological function as a tumour-suppressing protein. This milestone constitutes a turning point in the short life of this protein. Protein p53 plays a fundamental role in the mechanisms the cell uses to respond to damage or mutation in the genome. There is, therefore, a correlation between deletions or mutations in the p53 gene and the development of some kinds of cancer; additionally, increases in the protein levels of its native form have been reported in pathologies where apoptotic processes are high.
CONCLUSIONS Protein p53 plays an essential role in the mechanisms by which the cell responds to damage or mutation in the genome. It can activate two signalling mechanisms that lead either to stopping the cell cycle or to the death of the cell due to apoptosis if the cell cannot repair the damage to the genome. There is a correlation between its deletions and mutations and the development of cancer, and increases in its native form have been described in pathologies where apoptotic processes are high, as is the case of some neurodegenerative diseases.
KeywordsCancerCell cycleGenomeMitochondriaNeurodegenerationTranscription factorsCategoriesCáncer y tumoresNeurociencia básicaNeurodegeneración
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