Translational approaches to restoring mitochondrial function in Parkinson's disease

Abstract

There is strong evidence of a key role for mitochondrial dysfunction in both sporadic and all forms of familial Parkinson's disease (PD). However, none of the clinical trials carried out with putative mitochondrial rescue agents have been successful. Firm establishment of a wet biomarker or a reliable readout from imaging studies detecting mitochondrial dysfunction and reflecting disease progression is also awaited. We will provide an overview of our current knowledge about mitochondrial dysfunction in PD and related drug screens. We will also summarise previously undertaken mitochondrial wet biomarker studies and relevant imaging studies with particular focus on 31P-MRI spectroscopy. We will conclude with an overview of clinical trials which tested putative mitochondrial rescue agents in PD patients.

Neuroprotective Effects of Cryptotanshinone in a Direct Reprogramming Model of Parkinson’s Disease

“…Multiple reports suggest that the cause of PD involves alterations in diverse cellular processes, such as mitochondrial functions, DA regulation, calcium homeostasis, proteostasis, and autophagy-lysosomal pathways [ 2 , 3 ]. Although the exact mechanisms of PD are still unclear, previous studies have shown that cellular protection through modulation of mitochondria would be effective in treating PD [ 4 , 5 , 6 ].…”

Caloric restriction and redox homeostasis in various regions of aging male rat brain: Is caloric restriction still worth trying even after early-adulthood?

“…Although the human brain only accounts for nearly 2% of the body mass, via mitochondrial respiration, it consumes 15%–20% of the total fuel to run the entire body (Cobley, Fiorello, & Bailey, ). In aging process, injured mitochondria become less efficient, producing less ATP and more reactive oxygen species (ROS) (Mortiboys et al, ; Zorov, Juhaszova, & Sollott, ). Even though we still do not fully know how we age, one of the theories in the area to clarify this phenomenon, the free radical theory, uses mitochondria and ROS to explain this lifelong process (Kirkwood & Austad, ).…”

“…In aging process, injured mitochondria become less efficient, producing less ATP and more reactive oxygen species (ROS) (Mortiboys et al, 2018;Zorov, Juhaszova, & Sollott, 2014). Even though we still do not fully know how we age, one of the theories in the area to clarify this phenomenon, the free radical theory, uses mitochondria and ROS to explain this lifelong process (Kirkwood & Austad, 2000).…”

Special Issue on ‘ROS and mitochondria in nervous system function and disease’

“…Mortiboys et al . review the current state of translational approaches in restoring mitochondrial function in Parkinson's disease. In addition, Kang et al .…”

“…Mortiboys et al [14] review the current state of translational approaches in restoring mitochondrial function in Parkinson's disease. In addition, Kang et al [15] discuss the current understanding of the role of TFAM, a mitochondrial DNA binding protein and transcription factor, in common neurodegenerative diseases.…”