Native DIGE proteomic analysis of mitochondria from substantia nigra and striatum during neuronal degeneration and its compensation in an animal model of early Parkinson’s disease

Kuter, Katarzyna; Kratochwil, Manuela; Marx, Sven‐Hendric; Hartwig, Sonja; Lehr, S; Sugawa, M.; Dencher, Norbert A.

doi:10.1080/13813455.2016.1197948

Cited by 11 publications

(6 citation statements)

References 66 publications

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“…Studies have implicated DPYSL2 in the regulation of neuron guidance, growth, polarity [67], and synaptic signalling [68,69]. Additionally, altered DPYSL2 levels are associated with neurodegenerative diseases, as well as with neuropathic pain [69][70][71]. We previously reported a significant decrease in the gene expression of Dpysl2 in the sciatic nerves of db/ db neuropathic mice compared to normal controls [43].…”

Section: Discussionmentioning

confidence: 92%

Genome-wide DNA methylation profiling of human diabetic peripheral neuropathy in subjects with type 2 diabetes mellitus

et al. 2019

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DNA methylation is an epigenetic mechanism important for the regulation of gene expression, which plays a vital role in the interaction between genetic and environmental factors. Aberrant epigenetic changes are implicated in the pathogenesis of diabetes and diabetic complications, but the role of DNA methylation in diabetic peripheral neuropathy (DPN) is not well understood. Therefore, our aim in this study was to explore the role of DNA methylation in the progression of DPN in type 2 diabetes. We compared genome-wide DNA methylation profiles of human sural nerve biopsies from subjects with stable or improving nerve fibre counts to biopsies from subjects with progressive loss of nerve fibres. Nerve fibre counts were determined by comparing myelinated nerve fibre densities between an initial and repeat biopsy separated by 52 weeks. Subjects with significant nerve regeneration (regenerators) and subjects with significant nerve degeneration (degenerators) represent the two extreme DPN phenotypes. Using reduced representation bisulfite sequencing, we identified 3,460 differentially methylated CpG dinucleotides between the two groups. The genes associated with differentially methylated CpGs were highly enriched in biological processes that have previously been implicated in DPN such as nervous system development, neuron development, and axon guidance, as well as glycerophospholipid metabolism and mitogen-activated protein kinase (MAPK) signalling. These findings are the first to provide a comprehensive analysis of DNA methylation profiling in human sural nerves of subjects with DPN and suggest that epigenetic regulation has an important role in the progression of this prevalent diabetic complication.

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Section: Discussionmentioning

confidence: 92%

Genome-wide DNA methylation profiling of human diabetic peripheral neuropathy in subjects with type 2 diabetes mellitus

et al. 2019

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“…The assay was performed on crude mitochondrial tissue fractions isolated as published before (Kuter et al . ,b), according to kit K716 and manufacturer protocol (BioVision). Protein amounts in samples were determined using the Bradfordt test.…”

Section: Methodsmentioning

confidence: 99%

Astrocyte support is important for the compensatory potential of the nigrostriatal system neurons during early neurodegeneration

Kuter

Olech

Głowacka

et al. 2018

Journal of Neurochemistry

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Glial pathology precedes symptoms of Parkinson's disease and multiple other neurodegenerative diseases. Prolonged impairment of astrocytic functions could increase the vulnerability of dopaminergic neurons in the substantia nigra (SN), accelerate their degeneration and affect ability to compensate for partial degeneration at the presymptomatic stages of the disease. The aim of this study was to investigate the astrocyte depletion in the SN, its impact on the dopaminergic system functioning and multiple markers of energy metabolism during the early stages of neurodegeneration and compensation. We induced death of 30% of astrocytes by chronic infusion of fluorocitrate (FC) into the SN, simultaneously activating microglia response but sparing the dopaminergic neurons. The FC effect was reversible after toxin withdrawal. Dopaminergic neurons were killed by 6-hydroxydopamine causing transient locomotor disability, reversed with time showing compensatory potential. Death of astrocytes diminished the capability of the dopaminergic system to compensate for the degeneration of neurons and caused a local energy deprivation by decreasing lactate and glycogen amount. Studied markers suggest a shift in the usage of energy substrates, via increased glycogenolysis and glycolysis markers, ketone bodies availability and fatty acid transport in remaining cells. Peroxisome proliferator-activated receptor-gamma coactivator 1a (PGC-1alpha) and AMPactivated protein kinase (AMPK), the energy sensors, showed different regulation between the cell-types. Increased neuronal expression of carnitine palmitoyltransferase 1c could play a role in the adaptation to metabolic stress in response to glia dysfunction. Astrocyte energetic support is one of the essential factors for neuronal compensatory mechanisms of dopaminergic system and might have a leading role in the presymptomatic Parkinson's disease stages. Abbreviations used: AMPK, AMP-activated protein kinase, catalytic subunit alpha; b-HB, ß-hydroxybutyrate; CPT1a, glial carnitine palmitoyltransferase 1a; CPT1c, neuronal carnitine palmitoyltransferase 1c; GS, glutamine synthetase; mACO, mitochondrial aconitase; PDK2, pyruvate dehydrogenase kinase 2; PGC-1a, peroxisome proliferatoractivated receptor-gamma coactivator 1a; PKM2, pyruvate kinase M2.

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“…Dihydropyrimidinase-related protein 2 (DPYSL2), which is important for axon outgrowth and regeneration (Sun and Cavalli, 2010), first decreased and then gradually recovered in this model. Moreover, axon growth and mitochondrial transport-related proteins (e.g., dynein, dynamin, and myosin) were also overexpressed (Kuter et al, 2016). Thus, a potential therapy to promote axon regeneration would be to enhance the expression of mitochondrial transport-related proteins.…”

Section: Treatmentmentioning

confidence: 99%

Mitochondrial Behavior in Axon Degeneration and Regeneration

Wang

Huang

Shang

et al. 2021

Front. Aging Neurosci.

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Mitochondria are organelles responsible for bioenergetic metabolism, calcium homeostasis, and signal transmission essential for neurons due to their high energy consumption. Accumulating evidence has demonstrated that mitochondria play a key role in axon degeneration and regeneration under physiological and pathological conditions. Mitochondrial dysfunction occurs at an early stage of axon degeneration and involves oxidative stress, energy deficiency, imbalance of mitochondrial dynamics, defects in mitochondrial transport, and mitophagy dysregulation. The restoration of these defective mitochondria by enhancing mitochondrial transport, clearance of reactive oxidative species (ROS), and improving bioenergetic can greatly contribute to axon regeneration. In this paper, we focus on the biological behavior of axonal mitochondria in aging, injury (e.g., traumatic brain and spinal cord injury), and neurodegenerative diseases (Alzheimer's disease, AD; Parkinson's disease, PD; Amyotrophic lateral sclerosis, ALS) and consider the role of mitochondria in axon regeneration. We also compare the behavior of mitochondria in different diseases and outline novel therapeutic strategies for addressing abnormal mitochondrial biological behavior to promote axonal regeneration in neurological diseases and injuries.

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Native DIGE proteomic analysis of mitochondria from substantia nigra and striatum during neuronal degeneration and its compensation in an animal model of early Parkinson’s disease

Cited by 11 publications

References 66 publications

Genome-wide DNA methylation profiling of human diabetic peripheral neuropathy in subjects with type 2 diabetes mellitus

Genome-wide DNA methylation profiling of human diabetic peripheral neuropathy in subjects with type 2 diabetes mellitus

Astrocyte support is important for the compensatory potential of the nigrostriatal system neurons during early neurodegeneration

Mitochondrial Behavior in Axon Degeneration and Regeneration

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