Lrk2 Case Study - 1616 Words

LRRK2 Kinase activity of mutant LRRK2 has been shown to mediate neuronal toxicity and cell death in PD (Smith et al., 2006). The BRAF kinase which is believed to cause a significant proportion of melanoma is similar to the kinase domain of LRRK2, which is known to drive a significant proportion of malignant melanoma (Bishop et al., 2009; Flaherty et al., 2010; Flemming et al., 2010; Paisan Ruiz et al., 2010; Shen J et al., 2004), implying that there could be functional analogies between the activation of the BRAF kinase in melanoma and activation of LRRK2 kinase in PD-associated neurodegeneration (Paisn-Ruiz et al., 2010) DJ-1 DJ-1 was initially identified as an oncogene. It has been reported that mutations in DJ1 causes familial PD. DJ-1†¦show more content†¦It is expressed in melanoma cell lines, and is involved in melanocyte survival by detoxification of the intermediates formed as a result of melanogenesis (Harteneck et al., 2005; Iuga et al., 2007; McNeill MS et al., 2007 ). The heterozygous variant of TRPM7 has been found in some PD patients with dementia and some Guamanian patients (Hermosura et al., 2007). Inhibition of melanin synthesis prevents melanophore cell death in TRPM7 mutants therefore providing a possible clue that can explain the increased risk of PD and ALS in melanoma patients (Bertoni JM et al., 2010) Tumor suppressor gene p53 The tumor suppressor gene p53 plays an important role in human neurodegenerative disorders such as PD. Therefore chemical inhibitors of that activate p53 may be effective in suppressing the neurodegenerative process in PD (Stretch et al., 1991). Loss of p53 function, that has been identified in a variety of human tumor types such as melanoma (Duan W et al, 2002). Therefore it is possible that the risk for PD might be