Editorial: Mitochondrial Dysfunction and Neurodegeneration

Tapias, Vı́ctor

doi:10.3389/fnins.2019.01372

Cited by 29 publications

(15 citation statements)

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“…Mitochondrial impairments have been associated to several pathologies not only limited to metabolic diseases or myopathies, but including cancer (Vyas et al, 2016;Denisenko et al, 2019), pulmonary hypertension (Chen et al, 2019) and neurodegenerative disorders such as Alzheimer's and Parkinson's disease (Kim and Mook-Jung, 2019;Tapias, 2019). Thus, further understanding of mitochondrial surveillance mechanisms might help to establish therapeutic interventions for treatment of mitochondrial pathologies.…”

Section: Future Perspectivesmentioning

confidence: 99%

Mitochondrial Quality Control Governed by Ubiquitin

Ravanelli

Brave

Hoppe

2020

Front. Cell Dev. Biol.

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Mitochondria are essential organelles important for energy production, proliferation, and cell death. Biogenesis, homeostasis, and degradation of this organelle are tightly controlled to match cellular needs and counteract chronic stress conditions. Despite providing their own DNA, the vast majority of mitochondrial proteins are encoded in the nucleus, synthesized by cytosolic ribosomes, and subsequently imported into different mitochondrial compartments. The integrity of the mitochondrial proteome is permanently challenged by defects in folding, transport, and turnover of mitochondrial proteins. Therefore, damaged proteins are constantly sequestered from the outer mitochondrial membrane and targeted for proteasomal degradation in the cytosol via mitochondrial-associated degradation (MAD). Recent studies identified specialized quality control mechanisms important to decrease mislocalized proteins, which affect the mitochondrial import machinery. Interestingly, central factors of these ubiquitindependent pathways are shared with the ER-associated degradation (ERAD) machinery, indicating close collaboration between both tubular organelles. Here, we summarize recently described cellular stress response mechanisms, which are triggered by defects in mitochondrial protein import and quality control. Moreover, we discuss how ubiquitindependent degradation is integrated with cytosolic stress responses, particularly focused on the crosstalk between MAD and ERAD.

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Section: Future Perspectivesmentioning

confidence: 99%

Mitochondrial Quality Control Governed by Ubiquitin

Ravanelli

Brave

Hoppe

2020

Front. Cell Dev. Biol.

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“…The development of new strategies based on PLGA NPs to enhance brain drug delivery is of great interest in NDD therapy [ 45 ]. Indeed, even if different pathologies are included in NDD, they all share common mechanisms such as mitochondrial or oxidative injury, neuro-inflammation, apoptosis, and protein aggregation, which contribute to neuronal loss mainly by the intrinsic mitochondrial apoptotic pathway ( Figure 2 ) [ 46 , 47 ]. The mitochondria complexes and mitochondrially located monoamine oxidase B (MAO-B) are involved in the nitrogen and reactive oxygen species (ROS) production.…”

Section: Plga Nps For Neuroprotective Drug Delivery In Neurological Disorder Therapymentioning

confidence: 99%

PLGA-Based Nanoparticles for Neuroprotective Drug Delivery in Neurodegenerative Diseases

et al. 2021

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Treatment of neurodegenerative diseases has become one of the most challenging topics of the last decades due to their prevalence and increasing societal cost. The crucial point of the non-invasive therapeutic strategy for neurological disorder treatment relies on the drugs’ passage through the blood-brain barrier (BBB). Indeed, this biological barrier is involved in cerebral vascular homeostasis by its tight junctions, for example. One way to overcome this limit and deliver neuroprotective substances in the brain relies on nanotechnology-based approaches. Poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) are biocompatible, non-toxic, and provide many benefits, including improved drug solubility, protection against enzymatic digestion, increased targeting efficiency, and enhanced cellular internalization. This review will present an overview of the latest findings and advances in the PLGA NP-based approach for neuroprotective drug delivery in the case of neurodegenerative disease treatment (i.e., Alzheimer’s, Parkinson’s, Huntington’s diseases, Amyotrophic Lateral, and Multiple Sclerosis).

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“…The most relevant alterations include elevated oxidative stress (that can damage mitochondrial respiratory complex expression and/or activity); perturbations in mitochondrial dynamics; alterations in mitochondrial transport within axons; mitophagy; accumulation of somatic mtDNA mutations; impaired quality control mechanisms leading to the accumulation of defective mitochondria; defective calcium (Ca 2+ ) homeostasis and signaling. It was postulated that all of these processes may result in neuronal death ( 68 ). In post-mortem substantia nigra from PD patients it was found a decrease in CI activity, reduction of ATP levels, increments of ROS and impaired mitochondrial membrane potential leading to Ca 2+ -mediated damage ( 69 ), while in the caudate nucleus increased variability in mitochondrial morphology was also observed ( 70 ).…”

Section: Mitochondrial Dysfunction and Scs Organization And Activity mentioning

confidence: 99%