In Vivo Mitochondrial Function in Idiopathic and Genetic Parkinson’s Disease

Abstract

Parkinson's disease (PD) is associated with brain mitochondrial dysfunction. High-energy phosphates (HEPs), which rely on mitochondrial functioning, may be considered potential biomarkers for PD. Phosphorus magnetic resonance spectroscopy ( 31 P-MRS) is a suitable tool to explore in vivo cerebral energetics. We considered 10 31 P-MRS studies in order to highlight the main findings about brain energetic compounds in patients affected by idiopathic PD and genetic PD. The studies investigated several brain areas such as frontal lobes, occipital lobes, temporoparietal cortex, visual cortex, midbrain, and basal ganglia. Resting-state studies reported contrasting results showing decreased as well as normal or increased HEPs levels in PD patients. Functional studies revealed abnormal PCr + βATP levels in PD subjects during the recovery phase and abnormal values at rest, during activation and recovery in one PD subject with PINK1 gene mutation suggesting that mitochondrial machinery is more impaired in PD patients with PINK1 gene mutation. PD is characterized by energetics impairment both in idiopathic PD as well as in genetic PD, suggesting that mitochondrial dysfunction underlies the disease. Studies are still sparse and sometimes contrasting, maybe due to different methodological approaches. Further studies are needed to better assess the role of mitochondria in the PD development.

Effects of Treadmill Exercise on Neural Mitochondrial Functions in Parkinson’s Disease: A Systematic Review of Animal Studies

“…In the current included studies, the abnormal expression of complex II, complex III, complex IV, and complex V in Parkinson's disease were varied [15,20,21,23,26]. Consistent with those data, previous studies showed that the alterations of complexes II-V in Parkinson's disease were diverse, which seemed to be remodeled in response to the complex I deficits [5,11,30]. The current included studies showed that treadmill training normalized the levels of neural mitochondrial complexes II-V, suggesting that treadmill training prevented the abnormal remodeling of complexes II-V in Parkinson's disease.…”

“…To establish this issue, it is necessary to have an efficient method to measure the change of Parkinson's disease mechanisms during and after treadmill training. Recently, the evidence has suggested that 31 phosphorus-magnetic resonance spectroscopy ( 31 P-MRS) is a promised approach for the evaluation of mitochondrial function in Parkinson's disease patients in both the rest-stage and moving-stage [5]. Although the application of 31…”

“…Recently, neural mitochondrial respiratory deficiency has emerged as a central hallmark of Parkinsonian etiology [4,5]. In PD, the electron transport system of the neural mitochondria is impaired, mainly characterized by mitochondrial complex I deficit, cytochrome c release, and ATP depletion [6].…”

Targeting Mitochondrial Impairment in Parkinson's Disease: Challenges and Opportunities

“…Neuroimaging studies on mitochondrial impairment in PD are still scarce and lack intra-site reliability (e.g., by distinct hardware requirements), which is one major prerequisite for theranostic-accompanied drug trials (Dossi et al, 2019). The ongoing development of quantitative MRI/MRSI sequences and dual-calibrated fMRI (for MRI-based oximetry) will more than likely overcome the problem of inter-site reliability (Lara et al, 1993;Germuska et al, 2019).…”

“…often show tissue-specific expression patterns and therefore lack biological interpretability in peripheral blood cells, e.g., peripheral monoclonal blood cells (PMBCs; Dossi et al, 2019;He et al, 2019). The determination of mtDNA mutation load is altered by the different proliferation rates of distinct cell types, which hinders the insights gathered from PMBCs to assess neuronal dysfunction (O'Callaghan et al, 2015).…”