Mitochondrial SIRT3 confers neuroprotection in Huntington's disease by regulation of oxidative challenges and mitochondrial dynamics

Naia, Luana; Carmo, Catarina; Campesan, Susanna; Fão, Lígia; Cotton, Victoria E.; Valero, Jorge; Lopes, Carla; Rosenstock, Tatiana R.; Giorgini, Flaviano; Rego, A. Cristina

doi:10.1016/j.freeradbiomed.2020.11.031

Cited by 54 publications

(38 citation statements)

References 63 publications

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“…Mitochondrial morphology was analyzed using Macros designed in Fiji (ImageJ, National Institute of Health, Bethesda, MA, USA) by Dr. Jorge Valero (CNC, University of Coimbra, presently at Achucarro—Basque Centre for Neuroscience, Spain) as described by Naia et al [ 28 ]. We obtained the roundness, which is a two-dimensional index of mitochondrial sphericity (the relation between mitochondrial area and its major axis), aspect ratio that measures length (the ratio between the major and minor axis of mitochondria), as well as form factor, which is a measure of the degree of mitochondria branching (FF = Perimeter2/4π × area).…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial Alterations in Fibroblasts of Early Stage Bipolar Disorder Patients

Marques

Resende²,

Silva³

et al. 2021

Biomedicines

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This study aims to evaluate whether mitochondrial changes occur in the early stages of bipolar disorder (BD). Using fibroblasts derived from BD patients and matched controls, the levels of proteins involved in mitochondrial biogenesis and dynamics (fission and fusion) were evaluated by Western Blot analysis. Mitochondrial membrane potential (MMP) was studied using the fluorescent probe TMRE. Mitochondrial morphology was analyzed with the probe Mitotracker Green and mitophagy was evaluated by quantifying the co-localization of HSP60 (mitochondria marker) and LC3B (autophagosome marker) by immunofluorescence. Furthermore, the activity of the mitochondrial respiratory chain and the glycolytic capacity of controls and BD patients-derived cells were also studied using the Seahorse technology. BD patient-derived fibroblasts exhibit fragmented mitochondria concomitantly with changes in mitochondrial dynamics and biogenesis in comparison with controls. Moreover, a decrease in the MMP and increased mitophagy was observed in fibroblasts obtained from BD patients when compared with control cells. Impaired energetic metabolism due to inhibition of the mitochondrial electron transport chain (ETC) and subsequent ATP depletion, associated with glycolysis stimulation, was also a feature of BD fibroblasts. Overall, these results support the fact that mitochondrial disturbance is an early event implicated in BD pathophysiology that might trigger neuronal changes and modification of brain circuitry.

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Section: Methodsmentioning

confidence: 99%

Mitochondrial Alterations in Fibroblasts of Early Stage Bipolar Disorder Patients

Marques

Resende²,

Silva³

et al. 2021

Biomedicines

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show abstract

“…Deficiency of SIRT3, known as a mitochondrial deacetylase, is a significant cause of metabolic syndrome. SIRT3 regulates the functioning of critical mitochondrial proteins by deacetylation [64,65]. Tyagi et al [66] stated that deficiency of SIRT3 increases the formation of amyloid plaques and induces neuroinflammation in the brain.…”

Section: Metabolic Impairment and Admentioning

confidence: 99%

Crosstalk between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies

et al. 2021

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The gut microbiota (GM) represents a diverse and dynamic population of microorganisms and about 100 trillion symbiotic microbial cells that dwell in the gastrointestinal tract. Studies suggest that the GM can influence the health of the host, and several factors can modify the GM composition, such as diet, drug intake, lifestyle, and geographical locations. Gut dysbiosis can affect brain immune homeostasis through the microbiota–gut–brain axis and can play a key role in the pathogenesis of neurodegenerative diseases, including dementia and Alzheimer’s disease (AD). The relationship between gut dysbiosis and AD is still elusive, but emerging evidence suggests that it can enhance the secretion of lipopolysaccharides and amyloids that may disturb intestinal permeability and the blood–brain barrier. In addition, it can promote the hallmarks of AD, such as oxidative stress, neuroinflammation, amyloid-beta formation, insulin resistance, and ultimately the causation of neural death. Poor dietary habits and aging, along with inflammatory responses due to dysbiosis, may contribute to the pathogenesis of AD. Thus, GM modulation through diet, probiotics, or fecal microbiota transplantation could represent potential therapeutics in AD. In this review, we discuss the role of GM dysbiosis in AD and potential therapeutic strategies to modulate GM in AD.

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“…In different HD models, several reports have shown the increase of oxidative stress and deficits of mitochondria in this disease [ 23 – 25 ]. These deficits include the impairments on mitochondrial biogenesis, dynamics, membrane potential, electron transport chains, adenosine triphosphate (ATP) productions, etc., and finally affect cellular functions, neuropathogenesis and clinic symptoms [ 24 – 27 ]. Due to the critical roles of mitochondrial functions in HD pathogenesis, several treatments targeting on this aspect have been demonstrated.…”

Section: Huntington’s Diseasementioning

confidence: 99%

“…Due to the critical roles of mitochondrial functions in HD pathogenesis, several treatments targeting on this aspect have been demonstrated. For example, activation of mitochondria-related genes, such as Sirtuin 3 (SIRT3), Peroxisome proliferator-activated receptor gamma co-activator-1 alpha (PGC1alpha), Uncoupling protein (UCP), has shown to alleviate HD symptoms in different models [ 23 , 24 , 28 ], highly suggesting improvement of mitochondrial functions is an important therapeutical strategy for HD (Fig. 1 ).…”

Section: Huntington’s Diseasementioning

confidence: 99%

The regulatory roles of microRNAs toward pathogenesis and treatments in Huntington's disease

et al. 2021

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Huntington’s disease (HD) is one of neurodegenerative diseases, and is defined as a monogenetic disease due to the mutation of Huntingtin gene. This disease affects several cellular functions in neurons, and further influences motor and cognitive ability, leading to the suffering of devastating symptoms in HD patients. MicroRNA (miRNA) is a non-coding RNA, and is responsible for gene regulation at post-transcriptional levels in cells. Since one miRNA targets to several downstream genes, it may regulate different pathways simultaneously. As a result, it raises a potential therapy for different diseases using miRNAs, especially for inherited diseases. In this review, we will not only introduce the update information of HD and miRNA, but also discuss the development of potential miRNA-based therapy in HD. With the understanding toward the progression of miRNA studies in HD, we anticipate it may provide an insight to treat this devastating disease, even applying to other genetic diseases.

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Mitochondrial SIRT3 confers neuroprotection in Huntington's disease by regulation of oxidative challenges and mitochondrial dynamics

Cited by 54 publications

References 63 publications

Mitochondrial Alterations in Fibroblasts of Early Stage Bipolar Disorder Patients

Mitochondrial Alterations in Fibroblasts of Early Stage Bipolar Disorder Patients

Crosstalk between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies

The regulatory roles of microRNAs toward pathogenesis and treatments in Huntington's disease

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