ABSTRACT
OPINION STATEMENT: We postulate that the frequently encountered grouping of different Parkinson disease (PD) variants into a single pathogenetic concept-rather than differentiation into its molecular subtypes-has hindered progress toward curative interventions. Parkinsonism is a clinical syndrome that in rare cases can be explained by a single genetic event or by a single environmental cause, thereby leading to monogenic PD and secondary parkinsonism, respectively. Under the former category, mutations in both alleles of the Parkin-encoding PARK2 gene leads to young-onset, autosomal recessive PD, in which neurodegeneration is restricted to dopamine-producing cells of the brainstem. Under the latter category, exposure to one of several environmental factors with neuroanatomic selectivity can cause rapid-onset, secondary parkinsonism most likely irrespective of the patient's age and genetic makeup. Sandwiched between these two extreme and rare types, the most common variant is referred to as late-onset, idiopathic PD. In extension of a disease model first proposed by Braak et al., we consider idiopathic PD the result of an encounter between one or several environmental triggers and one or more susceptibility alleles. Importantly, this interaction produces a pre-motor syndrome followed by the typical PD phenotype over a period of decades. In our opinion, this pathophysiological process should thus be viewed as a "complex disease." As is true for many complex human disorders, successful intervention for the common PD variant will likely occur when genetic leads as well as environmental contributors are targeted in parallel. However, successful proof-of-concept studies could arrive sooner, namely for select PD variants that can be attributed to a single genetic event and that are neuropathologically restricted. Therefore, the authors decided to focus the second portion of their review on treatment considerations regarding autosomal recessive PD cases that are caused by Parkin deficiency. We briefly draw attention to aspects of existing pharmacological and surgical therapies as they relate to the PARK2-linked variant; thereafter, we comment on new research avenues that are aimed at future therapeutic interventions to eventually slow or arrest the progression of a first variant of PD.
ABSTRACT
BACKGROUND: The p53 protein is expressed in pterygial epithelium, but the reported prevalence of its expression varies widely. Although the cause of this variation is unknown, several factors that may play a role have been investigated, but without conclusive findings. In the present study, the role of p53 codon 72 polymorphism, and that of both age and gender, on p53 expression in pterygium was investigated. METHODS: Pterygium and blood samples were harvested from 55 patients undergoing pterygium surgery. The pterygial specimens were studied immunohistochemically using antibodies against p53 protein. Polymerase chain reaction based analysis was used to resolve the p53 codon 72 polymorphism. RESULTS: Thirty-one (56.4%) of the 55 pterygial specimens were positive for p53 staining. The distributions of the three genotypes of the p53 codon 72 polymorphism in the p53-positive and -negative staining groups were not statistically different. The allelic frequency in the two groups was also not statistically different, nor was there any significant difference between both groups with respect to age or gender. CONCLUSIONS: A correlation between p53 codon 72 polymorphism, sex and gender and p53 protein expression was not found.
