Current status for development of disease–modifying therapies in Parkinson disease

Abstract

The introduction of dopamine replenishment therapy revolutionized the functional and vital prognosis of Parkinson disease (PD) ; however, there is currently no available treatment which can halt or reverse disease progression. Thus, there is an urgent need for the development of disease modifying therapy. From the late 20th to the early 21st century, the progress of molecular pathology, genetics and cell biology has provided a huge body of evidence in the molecular mechanisms of PD, and several pathophysiological cascades leading to neurodegeneration has been identified. Among them, many researches emphasized the neurodegenerative process elicited by the aberrant conformation change and metabolism of α–synuclein (αS), a major constituent of Lewy bodies. Furthermore, emerging evidence has suggested that aggregated αS can transfer from one cell to another, thereby affecting the normal physiological state of the neighboring neurons in a prion–like manner. These transmissible, extracellular αS species are ideal targets for the disease–modifying treatment including immunotherapy. In this review, I will overview the molecular structure and function of αS, its relevance to PD pathogenesis and will discuss the current status and future prospective of disease–modifying strategies in PD.