BBA - Molecular Basis of Disease
  Parkinson’s disease
Edited by T.M. Dawson, D.J. Moore and A.B. West
Volume 1792, Issue 7, Pages 585-740 (July 2009)

In this issue, Tom Gasser provides a unique insight into studies leading up to the identification of genes underlying Mendelian forms of PD and how to best interpret more recently described Mendelian genes that have more limited evidence of pathogenecity. In complement, Bras and Singleton focus on common genetic variation that may influence susceptibility to disease and how the application of genome wide association studies in PD promises to identify new genetic risk factors. The identification of genetic factors important in PD presents the opportunity for the development of model systems where biochemical pathways can be deciphered and therapeutic efficacies tested. Lim and Ng discuss genetic models so far developed and how they overlap (or diverge) from what might be considered a representative model of PD.

Waxman and Giasson discuss the current and sometimes conflicting theories underlying the molecular mechanisms of α-synuclein-induced neurodegeneration and highlight what is known about the unexpectedly enigmatic small protein.

Biskup and West discuss potential pathogenic mechanisms and LRRK2-linked pathways and the evidence thus far that LRRK2 activity is critical for the development of PD. The activity of α-synuclein and LRRK2 may be at the heart of disease pathogenesis, and Zhou and Przedborski consider the intracellular application of gene-engineered antibodies, or intrabodies, that might interfere with disease-associated activity.

Tsang and Chung discuss how oxidative and nitrosative stress might contribute to the pathogenesis of PD with a focus on how stress-related dysfunction of proteins implicated in familial PD may shed light on why markers of oxidative and nitrosative stress are consistently observed in disease. 

Cook and Petrucelli review the evidence that supports the possibility that the ubiquitin proteasome system may become compromised through pathogenic mechanisms responsible for PD.

Yacoubian and Standaert provide a comprehensive evaluation of efforts to identify neuroprotective therapies in PD, and how past trials that failed to demonstrate neuroprotection help to further understand the origins of the disease.

Wijeyekoon and Barker discuss neurorestorative approaches for PD based on the use of cell replacement therapy that may include embryonic stem cells and induced pluripotent stem cells. Finally, PD has been on the forefront with regard to the utilization of emergent technologies in gene therapy approaches. Björklund and Kirik comment on the different approaches for gene therapy that promise to provide both neuroprotection and neurorestoration in PD.

Jang and colleagues consider the role of influenza viruses and other viruses in the development of parkinsonism, a particularly timely discussion due to the continual emergence of new influenza strains. Jang and colleagues hypothesize that certain viral infections may predispose individuals with particular genetic backgrounds to PD.

Pavese and Brooks discuss past and future imaging methods to study both motor and nonmotor complications associated with PD. On a pathological level, Dr. Jellinger reviews the current staging of α-synuclein pathology in Lewy body disorders, including PD, Lewy body disease, and dementia with Lewy Bodies. He presents a strong argument that dementia in PD often does not correlate with proposed stages of Lewy body pathology, fundamentally highlighting that the pathogenic role of Lewy bodies has not yet been elucidated.

The reader should note that this collection of papers only represents a portion of the outstanding work ongoing in PD research. All the work highlighted here would not have been possible without the extensive body of work that preceded these studies. Due to space limitations and timing, it is not possible to acknowledge all the past and ongoing work in PD. We hope this special issue provides a taste of the excitement in this field and the opportunities for innovative therapies that are arising. Finally, we thank all the contributors for their timely contributions and the expert reviewers for their advice and guidance on these articles.