Pattern of Mitochondrial Respiration in Peripheral Blood Cells of Patients with Parkinson’s Disease

Abstract

Mitochondria are central in the pathogenesis of Parkinson’s disease (PD), as they are involved in oxidative stress, synaptopathy, and other immunometabolic pathways. Accordingly, they are emerging as a potential neuroprotection target, although further human-based evidence is needed for therapeutic advancements. This study aims to shape the pattern of mitochondrial respiration in the blood leukocytes of PD patients in relation to both clinical features and the profile of cerebrospinal fluid (CSF) biomarkers of neurodegeneration. Mitochondrial respirometry on the peripheral blood mononucleate cells (PBMCs) of 16 PD patients and 14 controls was conducted using Seahorse Bioscience technology. Bioenergetic parameters were correlated either with standard clinical scores for motor and non-motor disturbances or with CSF levels of α-synuclein, amyloid-β peptides, and tau proteins. In PD, PBMC mitochondrial basal respiration was normal; maximal and spare respiratory capacities were both increased; and ATP production was higher, although not significantly. Maximal and spare respiratory capacity was directly correlated with disease duration, MDS-UPDRS part III and Hoehn and Yahr motor scores; spare respiratory capacity was correlated with the CSF amyloid-β-42 to amyloid-β-42/40 ratio. We provided preliminary evidence showing that mitochondrial respiratory activity increases in the PBMCs of PD patients, probably following the compensatory adaptations to disease progression, in contrast to the bases of the neuropathological substrate.

Mitochondrial Bioenergy in Neural Disease: Huntington and Parkinson

“…In a recent work, PBMCs mitochondrial bioenergetics from PD patients was assessed by the Seahorse Bioscience technology, showing a peculiar pattern of mitochondrial respiration, including normal basal respiration, significant augmentation of the maximal respiratory capacity and spare respiratory capacity, and a tendency to higher ATP production. The increased spare respiratory capacity was found to follow the disease duration and the severity of motor disturbances, revealing some mitochondrial adaptations to the higher bioenergetics requirements occurring at later disease stages [219]. Similar, consistent findings of greater mitochondrial respiration were also observed in different cell lines obtained from PD patients, such as lymphoblasts (immortalized blood lymphocyte-derived cells) [220] and fibroblasts [221,222].…”

Mitochondrial Bioenergy in Neural Disease: Huntington and Parkinson

“…The results showed a peculiar pattern of mitochondrial respiration, including normal basal respiration, significant augmentation of the maximal respiratory and spare respiratory capacity, and a tendency to increase ATP production. The increased spare respiratory capacity was found to follow the disease duration and the severity of motor disturbances, revealing some mitochondrial adaptations to the higher bioenergetics requirements occurring at later disease stages [ 214 ]. Similarly, consistent findings of greater mitochondrial respiration were also observed in different cell lines obtained from PD patients, such as lymphoblasts (immortalized blood lymphocytederived cells) [ 215 ] and fibroblasts [ 216 217 ].…”

Trimetazidine Improves Mitochondrial Dysfunction in SOD1G93A Cellular Models of Amyotrophic Lateral Sclerosis through Autophagy Activation

“…As previously reported [ 69 ], all participants underwent venous blood sampling (20 mL) in the morning, after overnight fasting (morning drugs allowed). Blood was immediately processed to separate PBMCs through density gradient centrifugation with Ficoll-Hypaque (GE Healthcare Life Sciences, Little Chalfont, UK) according to standard procedures [ 69 ]. PBMCs were carefully frozen in cryoSFM medium and stored in liquid nitrogen.…”