Considerations regarding the etiology and future treatment of autosomal recessive versus idiopathic parkinson disease

15Citations
Citations of this article
51Readers
Mendeley users who have this article in their library.
Get full text

Abstract

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 commonPD 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. © Springer Science+Business Media, LLC 2012.

Cite

CITATION STYLE

APA

Kitada, T., Tomlinson, J. J., Ao, H. S., Grimes, D. A., & Schlossmacher, M. G. (2012, June). Considerations regarding the etiology and future treatment of autosomal recessive versus idiopathic parkinson disease. Current Treatment Options in Neurology. https://doi.org/10.1007/s11940-012-0175-8

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free