Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been hypothesized that oncogenesis and neurodegeneration may share common mechanistic foundations. Recent evidence now reveals a number of genes in which alteration leads to either carcinogenesis or neurodegeneration, depending on cellular context. Pathways that have emerged as having critical roles in both cancer and neurodegenerative disease include those involving genes such as PARK2, ATM, PTEN, PTPRD, and mTOR. A number of mechanisms have been implicated, and commonly affected cellular processes include cell cycle regulation, DNA repair, and response to oxidative stress. For example, we have recently shown that the E3 ubiquitin ligase PARK2 is mutated or deleted in many different human malignancies and helps drive loss on chromosome 6q25.2-27, a genomic region frequently deleted in cancers. Mutation in PARK2 is also the most common cause of juvenile Parkinson's disease. Mutations in PARK2 result in an upregulation of its substrate cyclin E, resulting in dysregulated entry into the cell cycle. In neurons, this process results in cell death, but in cycling cells, the result is a growth advantage. Thus, depending on whether the cell affected is a dividing cell or a post-mitotic neuron, responses to these alterations may differ, ultimately leading to varying disease phenotypes. Here, we review the substantial data implicating specific genes in both cancer and neurodegenerative disease.
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PMID:Genetic determinants at the interface of cancer and neurodegenerative disease. 2041 18

Epidemiological studies support a general inverse association between the risk of cancer development and Parkinson's disease (PD). In recent years however, increasing amount of eclectic evidence points to a positive association between PD and cancers through different temporal analyses and ethnic groups. This positive association has been supported by several common genetic mutations in SNCA, PARK2, PARK8, ATM, p53, PTEN, and MC1R resulting in cellular changes such as mitochondrial dysfunction, aberrant protein aggregation, and cell cycle dysregulation. Here, we review the epidemiological and biological advances of the past decade in the association between PD and cancers to offer insight on the recent and sometimes contradictory findings.
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PMID:The associations between Parkinson's disease and cancer: the plot thickens. 2650 19

Mitophagy is a selective process aimed at removing damaged or burned-out mitochondria; it is activated upon different stimuli and plays a fundamental role in preventing overproduction of reactive oxygen species (ROS) that might be generated by dysfunctional mitochondria. From this angle, mitophagy can be considered a fully-fledged antioxidant process. Such a surrogate antioxidant function is recently emerging, being shared among many molecular pathways and players that are usually not included among - and, formally, do not directly act as - antioxidants. ATM (ataxia telangiectasia mutated) is a prototype of this class of "neglected" antioxidants. In spite of its well-known role in DNA damage response, many phenotypes of ataxia telangiectasia (A-T) patients are, indeed, related to chronic oxidative stress, arguing for an additional antioxidant role of ATM. In a recent study, we discovered the mechanism through which ATM exerts antioxidant activity. In particular, we provided evidence that this involves ADH5/GSNOR (alcohol dehydrogenase 5 (class III), chi polypeptide), which, in turn, sustains mitophagy via PARK2 denitrosylation, and protects the cell from detrimental effects due to ROS.
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PMID:ATM plays antioxidant, boosting mitophagy via denitrosylation. 3329 42