Abstract
Neurodegenerative diseases are a heterogeneous, mostly age-associated group of disorders characterized by progressive neuronal loss, the most prevalent being Alzheimer disease. It is anticipated that, with continuously increasing life expectancy, these diseases will pose a serious social and health problem in the near feature. Meanwhile, however, their etiology remains largely obscure even though all possible novel clues are being thoroughly examined. In this regard, a concept has been proposed that p53, as a transcription factor controlling many vital cellular pathways including apoptosis, may contribute to neuronal death common to all neurodegenerative disorders. In this work, we review the research devoted to the possible role of p53 in the pathogenesis of these diseases. We not only describe aberrant changes in p53 level/activity observed in CNS regions affected by particular diseases but, most importantly, put special attention to the complicated reciprocal regulatory ties existing between p53 and proteins commonly regarded as pathological hallmarks of these diseases, with the ultimate goal to identify the primary element of their pathogenesis.
Highlights
P53 was discovered in 1979 and described as a protein involved in tumorigenesis [1, 2, 3]
The reviewed data leave no doubt that p53 activation is one of discriminative molecular features of neurodegenerative diseases
Increased p53 level is infallibly detectable in brain areas attained by a particular disease, in the corresponding brain areas of animal models and in neuronal cells isolated from these brains
Summary
P53 was discovered in 1979 and described as a protein involved in tumorigenesis [1, 2, 3]. The same phenomenon i.e., increase in p53 level and activity was observed in PD patient brains as well as in PD animal and cellular models [54]. A substantially higher level of p53 was detected in the affected brain areas of HD patients and disease animal models [40, 59] as well as in cells overexpressing mutated huntingtin [60].
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