Gene Therapeutic Approaches for the Treatment of Mitochondrial Dysfunction in Parkinson’s Disease

Abstract

Background. Mitochondrial dysfunction has been identified as a pathophysiological hallmark of disease onset and progression in patients with Parkinsonian disorders. Besides the overall emergence of gene therapies in treating these patients, this highly relevant molecular concept has not yet been defined as a target for gene therapeutic approaches. Methods. This narrative review will discuss the experimental evidence suggesting mitochondrial dysfunction as a viable treatment target in patients with monogenic and idiopathic Parkinson’s disease. In addition, we will focus on general treatment strategies and crucial challenges which need to be overcome. Results. Our current understanding of mitochondrial biology in parkinsonian disorders opens up the avenue for viable treatment strategies in Parkinsonian disorders. Insights can be obtained from primary mitochondrial diseases. However, substantial knowledge gaps and unique challenges of mitochondria-targeted gene therapies need to be addressed to provide innovative treatments in the future. Conclusions. Mitochondria-targeted gene therapies are a potential strategy to improve an important primary disease mechanism in Parkinsonian disorders. However, further studies are needed to address the unique design challenges for mitochondria-targeted gene therapies.

Exploring neurodegenerative disorders using advanced magnetic resonance imaging of the glymphatic system

“…Studies in mice have shown that the infusion of alpha-synuclein into the brain results in its clearance via the glymphatic system, and this clearance is reduced in mice lacking AQP4 channels ( 22 ). Interestingly, the proper functioning of the glymphatic system has also been linked to other pathophysiological hallmarks of PD, such as mitochondrial dysfunction ( 23 ). Here, bioenergetic disturbances can drive increased protein deposition and subsequent breakdown of the glymphatic system ( 9 ).…”