Lithium carbonate and coenzyme Q10 reduce cell death in a cell model of Machado-Joseph disease

Lopes‐Ramos, Camila M.; Pereira, Tiago Campos; Dogini, D.B.; Gilioli, Rovílson; Lopes‐Cendes, Íscia

doi:10.1590/1414-431x20165805

Cited by 11 publications

(10 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lithium carbonate and coenzyme Q10 led to a significant increase in cell viability, a reduction in the proportion of apoptotic cells and a decrease in aggregates in a MJD/SCA3 cell model (Lopes‐Ramos et al . ). Chou and collaborators tested T1‐11 (an adenosine A2A receptor agonist) and a synthetic analogue (JMF1907) in a MJD/SCA3 transgenic mouse model.…”

Section: Therapeutic Perspectivesmentioning

confidence: 97%

Machado–Joseph disease/spinocerebellar ataxia type 3: lessons from disease pathogenesis and clues into therapy

Matos

Almeida

Nóbrega

2018

Journal of Neurochemistry

127

View full text Add to dashboard Cite

Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is an incurable disorder, widely regarded as the most common form of spinocerebellar ataxia in the world. MJD/SCA3 arises from mutation of the ATXN3 gene, but this simple monogenic cause contrasts with the complexity of the pathogenic mechanisms that are currently admitted to underlie neuronal dysfunction and death. The aberrantly expanded protein product - ataxin-3 - is known to aggregate and generate toxic species that disrupt several cell systems, including autophagy, proteostasis, transcription, mitochondrial function and signalling. Over the years, research into putative therapeutic approaches has often been devoted to the development of strategies that counteract disease at different stages of cellular pathogenesis. Silencing the pathogenic protein, blocking aggregation, inhibiting toxic proteolytic processing and counteracting dysfunctions of the cellular systems affected have yielded promising ameliorating results in studies with cellular and animal models. The current review analyses the available studies dedicated to the investigation of MJD/SCA3 pathogenesis and the exploration of possible therapeutic strategies, focusing primarily on gene therapy and pharmacological approaches rooted on the molecular and cellular mechanisms of disease.

show abstract

Section: Therapeutic Perspectivesmentioning

confidence: 97%

Machado–Joseph disease/spinocerebellar ataxia type 3: lessons from disease pathogenesis and clues into therapy

Matos

Almeida

Nóbrega

2018

Journal of Neurochemistry

127

View full text Add to dashboard Cite

show abstract

“…Moreover, mice treated with pre-conditioned MSC showed a greater amelioration of motor and behavior performance, decreased neuronal death, and reduction of huntingtin aggregates in the striatum (Linares et al, 2016 ). This strategy could be used in other polyQ diseases where Lithium and VPA showed promising results (Saute et al, 2014 ; Esteves et al, 2015 ; Lei et al, 2016 ; Lopes-Ramos et al, 2016 ).…”

Section: Methods To Increase Msc’s Efficacy In Vivomentioning

confidence: 99%

Mesenchymal Stromal Cells’ Therapy for Polyglutamine Disorders: Where Do We Stand and Where Should We Go?

Barros

Marcelo

Silva

et al. 2020

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Polyglutamine (polyQ) diseases are a group of inherited neurodegenerative disorders caused by the expansion of the cytosine-adenine-guanine (CAG) repeat. This mutation encodes extended glutamine (Q) tract in the disease protein, resulting in the alteration of its conformation/physiological role and in the formation of toxic fragments/aggregates of the protein. This group of heterogeneous disorders shares common molecular mechanisms, which opens the possibility to develop a pan therapeutic approach. Vast efforts have been made to develop strategies to alleviate disease symptoms. Nonetheless, there is still no therapy that can cure or effectively delay disease progression of any of these disorders. Mesenchymal stromal cells (MSC) are promising tools for the treatment of polyQ disorders, promoting protection, tissue regeneration, and/or modulation of the immune system in animal models. Accordingly, data collected from clinical trials have so far demonstrated that transplantation of MSC is safe and delays the progression of some polyQ disorders for some time. However, to achieve sustained phenotypic amelioration in clinics, several treatments may be necessary. Therefore, efforts to develop new strategies to improve MSC’s therapeutic outcomes have been emerging. In this review article, we discuss the current treatments and strategies used to reduce polyQ symptoms and major pre-clinical and clinical achievements obtained with MSC transplantation as well as remaining flaws that need to be overcome. The requirement to cross the blood-brain-barrier (BBB), together with a short rate of cell engraftment in the lesioned area and low survival of MSC in a pathophysiological context upon transplantation may contribute to the transient therapeutic effects. We also review methods like pre-conditioning or genetic engineering of MSC that can be used to increase MSC survival in vivo , cellular-free approaches—i.e., MSC-conditioned medium (CM) or MSC-derived extracellular vesicles (EVs) as a way of possibly replacing the use of MSC and methods required to standardize the potential of MSC/MSC-derived products. These are fundamental questions that need to be addressed to obtain maximum MSC performance in polyQ diseases and therefore increase clinical benefits.

show abstract

“…However, there have been two studies supplementing CoQ10 in model systems of Machafdo-Joseph disease. In a cell model of Machado-Joseph disease, Lopes-Ramos et al [ 99 ] described the use of CoQ10 (10–30 uM) to increase cell viability in PC-12 cells expressing expanded ataxin-3 protein. In a second study using a transgenic mouse model of Machado-Joseph diseasew, Wu et al [ 100 ] reported supplementation with CoQ10 (1000 mg/kg/day for 7 months) reduced cerebellar degeneration and improved motor dysfunction.…”

Section: Late Onset Machado-joseph Diseasementioning

confidence: 99%

Coenzyme Q10: Role in Less Common Age-Related Disorders

Mantle

Hargreaves

2022

Antioxidants

View full text Add to dashboard Cite

In this article we have reviewed the potential role of coenzyme Q10 (CoQ10) in the pathogenesis and treatment of a number of less common age-related disorders, for many of which effective therapies are not currently available. For most of these disorders, mitochondrial dysfunction, oxidative stress and inflammation have been implicated in the disease process, providing a rationale for the potential therapeutic use of CoQ10, because of its key roles in mitochondrial function, as an antioxidant, and as an anti-inflammatory agent. Disorders reviewed in the article include multi system atrophy, progressive supranuclear palsy, sporadic adult onset ataxia, and pulmonary fibrosis, together with late onset versions of Huntington’s disease, Alexander disease, lupus, anti-phospholipid syndrome, lysosomal storage disorders, fibromyalgia, Machado-Joseph disease, acyl-CoA dehydrogenase deficiency, and Leber’s optic neuropathy.

show abstract

Lithium carbonate and coenzyme Q10 reduce cell death in a cell model of Machado-Joseph disease

Cited by 11 publications

References 41 publications

Machado–Joseph disease/spinocerebellar ataxia type 3: lessons from disease pathogenesis and clues into therapy

Machado–Joseph disease/spinocerebellar ataxia type 3: lessons from disease pathogenesis and clues into therapy

Mesenchymal Stromal Cells’ Therapy for Polyglutamine Disorders: Where Do We Stand and Where Should We Go?

Coenzyme Q10: Role in Less Common Age-Related Disorders

Contact Info

Product

Resources

About