Molecular pathways and genetic aspects of Parkinson’s disease: from bench to bedside

Abstract

Idiopathic Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by dopaminergic neuronal loss within the substantia nigra. The incidence and prevalence of PD is rising with an increasing aging population. PD is a slowly progressive condition and patients can develop debilitating motor and functional impairment. Current research has implicated oxidative stress, α-synucleinopathy and dysfunction of the ubiquitin–proteasome system in the pathogenesis of PD. A number of gene mutations have also been linked to the development of PD. The elucidation of these new molecular pathways has increased our knowledge of PD pathophysiology. This article reviews important molecular mechanisms and genetic causes implicated in the pathogenesis of PD, which has led to new areas of therapeutic drug research.

Keywords::

• α-synuclein
• autophagy
• DJ-1
• dopaminergic neurons
• genetics
• Lewy bodies
• LRRK2
• oxidative stress
• parkin
• Parkinson’s disease
• PINK1
• ubiquitin–proteasome system
• UCH-L1

Acknowledgements

M Di Napoli wishes to thank his colleagues and friends Thomas Schmidt-Glenewinkel, PhD, Department of Biological Sciences, Hunter College of CUNY, New York, NY10021, USA; and Jian Feng, PhD, Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY 14214, USA, for the useful and constructive discussions on several topics included in this article.

Financial & competing interests disclosure

D Stewart has received consultancy fees and honoraria from GlaxoSmithKline. He is a member of faculty of the Parkinson’s Academy, which is supported by an unrestricted educational grant from Boehringer Ingleheim. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Notes

L-DOPA: L-3,4-dihydroxyphenylalanine; REM: Rapid eye movement.