Investigate the relationship between PD progression and genetic polymorphisms in the following enzyme systems:
Monoamine Oxidase A and B (MAO-A and MAO-B)
Catechol-O-Methyltransferase (COMT)
Superoxide Dismutase (SOD)
Prolyl Endopeptidase (PE)
Understand the influence these polymorphisms may have on PD progression and treatment response.
REFERENCES
Enzyme
Polymorphism
MAO (Monoamine Oxidase)
MAO-B (rs1799836) polymorphism predicts putaminal DA turnover in early PD
rs179983 linked to high enzyme activity leading to higher intrinsic DA turnover
Demonstrated to constitute a risk factor for motor complications
COMT (Catechol-O-methyltransferase)
G allele of COMT rs6269 and COMT Haplotype 6 (GCCG for rs6269, rs4633, rs4818, and rs4680) may be associated with cognitive decline in patients with PD
rs4680 polymorphism is associated with PD risk in the Asian population
SOD (Superoxide Dismutase)
Unclear role of SOD polymorphisms in PD. More clinical evidence needed
PE (Prolyl Endopeptidase)
Unclear role of PE polymorphisms in PD. More clinical evidence needed
A Literature Review on the Influence of Enzyme Polymorphisms in Parkinson’s Disease Progression and Response to Interventions
Michael Schaefer, Cameron Humerickhouse, Jaqueline Pereira, Nhi Tran, Stephan Schmidt, Valvanera Vozmediano*
Center for Pharmacometrics & Systems Pharmacology, Department of Pharmaceutics, University of Florida, Orlando, FL
*Correspondence: valva@cop.ufl.edu
INTRODUCTION
Parkinson’s Disease (PD) is idiopathic and will affect more than 8.7 million people by 2030.
Progressive loss of dopaminergic neurons in Substantia Nigra Pars Compacta.
Enzymes with polymorphisms involved in PD may help clinicians customize a personalized pharmacotherapy.
Three multifaceted rating scales used to evaluate PD progression:
MDS-UPDRS
Hoehn and Yahr Staging
The Schwab and England Scale
CONCLUSIONS
Based on literature review, damage to dopaminergic neurons in the midbrain may dictate the pathway for PD progression.
Decreased dopamine production appears to modulate dopamine receptor functions, leading to altered downstream neuronal activity responsible for physiological symptoms.
Research supports that the increased turnover in dopamine breakdown leads to an increase in reactive oxygen species (ROS), causing neuronal inflammation and death.
Evidence suggests polymorphisms in MAO rs1799836 and COMT rs4680 may cause polar progression of PD based on dopamine turnover.
Studies support PE and SOD involvement in PD pathogenesis; however, the mechanisms remain unclear.