Role of Mitochondria in Neurodegenerative Diseases: The Dark Side of the “Energy Factory”

Correia, Sónia C.; Moreira, Paula I.

doi:10.1007/978-3-319-73344-9_11

Cited by 4 publications

(1 citation statement)

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“…Recent studies also demonstrated an important role of PGC-1α and of its targets in the formation and maintenance of hippocampal dendritic spines and synapses (Cheng et al, 2012). Impaired PGC-1α activity is emerging as a common underlying cause of mitochondrial dysfunction in neurodegenerative diseases such as AD, PD and Huntington disease (Correira, 2018). Pgc-1α (-/-) mice showed a decreased mitochondrial number and respiratory capacity and vacuolar lesions in the central nervous system (Leone et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Pioglitazone Improves Mitochondrial Organization and Bioenergetics in Down Syndrome Cells

et al. 2019

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Mitochondrial dysfunction plays a primary role in neurodevelopmental anomalies and neurodegeneration of Down syndrome (DS) subjects. For this reason, targeting mitochondrial key genes, such as PGC-1α/PPARGC1A , is emerging as a good therapeutic approach to attenuate cognitive disability in DS. After demonstrating the efficacy of the biguanide metformin (a PGC-1α activator) in a cell model of DS, we extended the study to other molecules that regulate the PGC-1α pathway acting on PPAR genes. We, therefore, treated trisomic fetal fibroblasts with different doses of pioglitazone (PGZ) and evaluated the effects on mitochondrial dynamics and function. Treatment with PGZ significantly increased mRNA and protein levels of PGC-1α. Mitochondrial network was fully restored by PGZ administration affecting the fission-fusion mitochondrial machinery. Specifically, optic atrophy 1 ( OPA1 ) and mitofusin 1 ( MFN1 ) were upregulated while dynamin-related protein 1 ( DRP1 ) was downregulated. These effects, together with a significant increase of basal ATP content and oxygen consumption rate, and a significant decrease of reactive oxygen species (ROS) production, provide strong evidence of an overall improvement of mitochondria bioenergetics in trisomic cells. In conclusion, we demonstrate that PGZ is able to improve mitochondrial phenotype even at low concentrations (0.5 μM). We also speculate that a combination of drugs that target mitochondrial function might be advantageous, offering potentially higher efficacy and lower individual drug dosage.

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Section: Discussionmentioning

confidence: 99%

Pioglitazone Improves Mitochondrial Organization and Bioenergetics in Down Syndrome Cells

et al. 2019

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Optimization in Mitochondrial Energetic Pathways

Benaroya¹

2021

Modern Trends in Structural and Solid Mechanics 3

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Brain energetics, mitochondria, and traumatic brain injury

Benaroya

2020

Reviews in the Neurosciences

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We review current thinking about, and draw connections between, brain energetics and metabolism, and between mitochondria and traumatic brain injury. Energy is fundamental to proper brain function. Its creation in a useful form for neurons and glia, and consistently in response to the brain’s high energy needs, is critical for physiological pathways. Dysfunction in the mechanisms of energy production is at the center of neurological and neuropsychiatric pathologies. We examine the connections between energetics and mitochondria – the organelle responsible for almost all the energy production in the cell – and how secondary pathologies in traumatic brain injury result from energetic dysfunction. This paper interweaves these topics, a necessity since they are closely coupled, and identifies where there exist a lack of understanding and of data. In addition to summarizing current thinking in these disciplines, our goal is to suggest a framework for the mathematical modeling of mechanisms and pathways based on optimal energetic decisions.

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Role of Mitochondria in Neurodegenerative Diseases: The Dark Side of the “Energy Factory”

Cited by 4 publications

References 178 publications

Pioglitazone Improves Mitochondrial Organization and Bioenergetics in Down Syndrome Cells

Pioglitazone Improves Mitochondrial Organization and Bioenergetics in Down Syndrome Cells

Optimization in Mitochondrial Energetic Pathways

Brain energetics, mitochondria, and traumatic brain injury

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