Sheila M Fleming1. 1. Department of Pharmaceutical Sciences, Northeast Ohio Medical University, 4209 State Route 44, RGE, Rootstown, OH, 44272, USA. sfleming1@neomed.edu.
Abstract
PURPOSE OF REVIEW: The purpose of the study was to discuss the main mechanisms associated with environmental and genetic factors that contribute to the development of Parkinson's disease (PD). RECENT FINDINGS: Novel genetic contributors to PD are being identified at a rapid pace in addition to novel environmental factors. The discovery of mutations in alpha-synuclein and leucine-rich repeat kinase 2 causing inherited forms of PD along with epidemiological, in vitro, and in vivo studies identifying herbicides, pesticides, and metals as risk factors have dramatically improved our understanding of mechanisms involved in the development of PD. However, at the same time, these discoveries have also added layers of complexity to the disease. Within the last several years, the genetics associated with PD has dominated the field in many ways; however, the majority of PD cases are likely due to different combinations of environmental exposures and genetic susceptibility. The most common toxicants used to model PD including rotenone, paraquat, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine have been shown to interact with many of the genes linked with PD such as alpha-synuclein. Therefore, an understanding of mechanisms common between genetic and environmental factors is essential for early detection and successful translation of potential therapies, which is the ultimate goal.
PURPOSE OF REVIEW: The purpose of the study was to discuss the main mechanisms associated with environmental and genetic factors that contribute to the development of Parkinson's disease (PD). RECENT FINDINGS: Novel genetic contributors to PD are being identified at a rapid pace in addition to novel environmental factors. The discovery of mutations in alpha-synuclein and leucine-rich repeat kinase 2 causing inherited forms of PD along with epidemiological, in vitro, and in vivo studies identifying herbicides, pesticides, and metals as risk factors have dramatically improved our understanding of mechanisms involved in the development of PD. However, at the same time, these discoveries have also added layers of complexity to the disease. Within the last several years, the genetics associated with PD has dominated the field in many ways; however, the majority of PD cases are likely due to different combinations of environmental exposures and genetic susceptibility. The most common toxicants used to model PD including rotenone, paraquat, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine have been shown to interact with many of the genes linked with PD such as alpha-synuclein. Therefore, an understanding of mechanisms common between genetic and environmental factors is essential for early detection and successful translation of potential therapies, which is the ultimate goal.
Authors: Anne Grünewald; Björn Arns; Philip Seibler; Aleksandar Rakovic; Alexander Münchau; Alfredo Ramirez; Carolyn M Sue; Christine Klein Journal: Neurobiol Aging Date: 2012-01-31 Impact factor: 4.673
Authors: Alfredo Ramirez; André Heimbach; Jan Gründemann; Barbara Stiller; Dan Hampshire; L Pablo Cid; Ingrid Goebel; Ammar F Mubaidin; Abdul-Latif Wriekat; Jochen Roeper; Amir Al-Din; Axel M Hillmer; Meliha Karsak; Birgit Liss; C Geoffrey Woods; Maria I Behrens; Christian Kubisch Journal: Nat Genet Date: 2006-09-10 Impact factor: 38.330
Authors: Amy B Manning-Bog; Alison L McCormack; Jie Li; Vladimir N Uversky; Anthony L Fink; Donato A Di Monte Journal: J Biol Chem Date: 2001-11-13 Impact factor: 5.157
Authors: Sven Geisler; Kira M Holmström; Diana Skujat; Fabienne C Fiesel; Oliver C Rothfuss; Philipp J Kahle; Wolfdieter Springer Journal: Nat Cell Biol Date: 2010-01-24 Impact factor: 28.824
Authors: Marie Y Davis; Catherine O Johnson; James B Leverenz; Daniel Weintraub; John Q Trojanowski; Alice Chen-Plotkin; Vivianna M Van Deerlin; Joseph F Quinn; Kathryn A Chung; Amie L Peterson-Hiller; Liana S Rosenthal; Ted M Dawson; Marilyn S Albert; Jennifer G Goldman; Glenn T Stebbins; Bryan Bernard; Zbigniew K Wszolek; Owen A Ross; Dennis W Dickson; David Eidelberg; Paul J Mattis; Martin Niethammer; Dora Yearout; Shu-Ching Hu; Brenna A Cholerton; Megan Smith; Ignacio F Mata; Thomas J Montine; Karen L Edwards; Cyrus P Zabetian Journal: JAMA Neurol Date: 2016-10-01 Impact factor: 18.302
Authors: Emily R Dirr; Osunde R Ekhator; Rachel Blackwood; John G Holden; Eliezer Masliah; Patrick J Schultheis; Sheila M Fleming Journal: Behav Brain Res Date: 2018-02-03 Impact factor: 3.332
Authors: Tianzhong Yang; Hongwei Tang; Harvey A Risch; Sarah H Olson; Gloria Peterson; Paige M Bracci; Steven Gallinger; Rayjean J Hung; Rachel E Neale; Ghislaine Scelo; Eric J Duell; Robert C Kurtz; Kay-Tee Khaw; Gianluca Severi; Malin Sund; Nick Wareham; Christopher I Amos; Donghui Li; Peng Wei Journal: Genet Epidemiol Date: 2020-08-10 Impact factor: 2.135