Lewy Body in Parkinson’s Disease: Causes or Scars of Neurodegeneration?

Parkinson’s disease is an age related neurodegenerative and movement disorder affecting 1-3% of individuals above the age of 60 years. Parkinson’s disease is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta and the accumulation of Lewy bodies in the surviving neurons. Lewy bodies are present in the central and sympathetic nervous systems, and it is a type of alpha-synucleinopathy, since alphasynuclein is the main constituent of Lewy body. The long disputed role of Lewy bodies in causing neurodegenerative diseases is poorly understood which stands as the main hurdle in developing neuroprotective therapies. In this review, we explore in depth the characteristics of Lewy body with a specific focus on alpha-synuclein, the protein chiefly responsible for the formation of Lewy bodies. We also throw light on the role of Lewy body in therapies for Parkinson’s disease and the relationship between dopamine homeostasis and protein misfolding. The discovery of several genes involved in Parkinson’s disease has led to the hypothesis that misfolding of proteins and dysfunction of the ubiquitin-proteasome pathway are vital to the neurodegenerative process. Mitochondrial dysfunction and oxidative stress have also been known to have an important role in affecting the dopaminergic neurons and in the accumulation of misfolded proteins. The body of evidence suggests that intermediate stage oligomers and protofibrils of alpha-synuclein are toxic and are part of the process of Lewy body formation. In vitro and in vivo drosophila and mouse work have shown that the pathway of protein misfolding and aggregation plays a key role in unraveling how, when and why neuronal apoptosis occurs. The factors influencing metabolism of alpha-synuclein and pathways influencing its aggregation would further enhance our understanding on the physiological role of Lewy body. Mini Review Lewy Body in Parkinson’s Disease: Causes or Scars of Neurodegeneration? Sushmitha Sathiyamoorthy1,3*, Xulin Tan1,3 and Eng-King Tan1,2,3* 1National Neuroscience Institute, Singapore 2Department of Neurology, Singapore General Hospital, Singapore 3Duke-NUS Graduate Medical School, Singapore *Corresponding author: Eng-King Tan and Sushmitha Sathiyamoorthy, National Neuroscience Institute, 308433, Singapore, Xulin Tan2, Duke-NUS Graduate Medical School, 169857, Singapore Received: March 28, 2014; Accepted: June 11, 2014; Published: June 14, 2014 Austin Publishing Group A