Parkin-linked Parkinson's disease: From clinical insights to pathogenic mechanisms and novel therapeutic approaches

Abstract

With over 7 million patients worldwide, Parkinson's disease (PD) is becoming more prevalent as life span and industrialization increase. While the majority of cases are sporadic and present in individuals over 65, inherited mutations in Parkin can manifest in individuals as young as teenagers. The involvement of Parkin in neurodegeneration has been widely investigated and its role in mitophagy is undeniable. In the recent years, however, additional functions of the protein are beginning to come to light, which in turn may influence the way patients harboring Parkin mutations are treated. In the present article, we discuss the clinical and genetic aspects of Parkin-linked PD. For this purpose, we consulted the MDSGene database, which comprises the literature of more than 1000 patients with Parkin mutations. In addition, we provide insight into Parkin's multifaceted role in mitochondrial clearance and maintenance. Finally, we discuss treatment strategies such as brain stimulation, small molecule drugs and dopaminergic cell replacement that could be tailored to improve the clinical phenotypes in Parkin-linked PD.

Keywords: Clinical trial; Gene-specific therapy; Inflammation; Mitochondria; Parkin; Parkinson’s disease.