Mitochondrial and metabolic-based protective strategies in Huntington’s disease: the case of creatine and coenzyme Q

Naia, Luana; Ribeiro, Maria J.; Rego, A. Cristina

doi:10.1515/rns.2011.060

Cited by 18 publications

(6 citation statements)

References 187 publications

(222 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent evidences suggest that impaired metabolism plays an important role in the pathogenesis of HD-affected individuals, in both central and peripheral tissues [1,8,51], and the ability of insulin and IGF-1 to promote cell survival has been increasingly proven [22][23][24]52] including in the context of HD [21,30]. However, the neuroprotective role achieved by insulin and IGF-1 has been questioned.…”

Section: Discussionmentioning

confidence: 99%

Activation of IGF-1 and Insulin Signaling Pathways Ameliorate Mitochondrial Function and Energy Metabolism in Huntington’s Disease Human Lymphoblasts

et al. 2014

Self Cite

View full text Add to dashboard Cite

Huntington's disease (HD) is an inherited neurodegenerative disease caused by a polyglutamine repeat expansion in the huntingtin protein. Mitochondrial dysfunction associated with energy failure plays an important role in this untreated pathology. In the present work, we used lymphoblasts obtained from HD patients or unaffected parentally related individuals to study the protective role of insulin-like growth factor 1 (IGF-1) versus insulin (at low nM) on signaling and metabolic and mitochondrial functions. Deregulation of intracellular signaling pathways linked to activation of insulin and IGF-1 receptors (IR,IGF-1R), Akt, and ERK was largely restored by IGF-1 and, at a less extent, by insulin in HD human lymphoblasts. Importantly, both neurotrophic factors stimulated huntingtin phosphorylation at Ser421 in HD cells. IGF-1 and insulin also rescued energy levels in HD peripheral cells, as evaluated by increased ATP and phosphocreatine, and decreased lactate levels. Moreover, IGF-1 effectively ameliorated O2 consumption and mitochondrial membrane potential (Δψm) in HD lymphoblasts, which occurred concomitantly with increased levels of cytochrome c. Indeed, constitutive phosphorylation of huntingtin was able to restore the Δψm in lymphoblasts expressing an abnormal expansion of polyglutamines. HD lymphoblasts further exhibited increased intracellular Ca(2+) levels before and after exposure to hydrogen peroxide (H2O2), and decreased mitochondrial Ca(2+) accumulation, being the later recovered by IGF-1 and insulin in HD lymphoblasts pre-exposed to H2O2. In summary, the data support an important role for IR/IGF-1R mediated activation of signaling pathways and improved mitochondrial and metabolic function in HD human lymphoblasts.

show abstract

Section: Discussionmentioning

confidence: 99%

Activation of IGF-1 and Insulin Signaling Pathways Ameliorate Mitochondrial Function and Energy Metabolism in Huntington’s Disease Human Lymphoblasts

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…The implication of OXCT1 in generation of ketone bodies, both in brain and peripheral tissues, suggests its important role in energy deficit in HD. Several lines of evidence have suggested metabolic deficits in HD (see review in Naia et al [35] ). Reduced ATP production has been shown in brain of presymptomatic and symptomatic HD mice [15] , [36] .…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Genes Involved in Metabolism and Oxidative Stress in the Peripheral Leukocytes of Huntington's Disease Patients

Chang¹,

Chen

Wu³

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

BackgroundHuntington's disease (HD) is caused by expanded CAG repeats encoding a polyglutamine tract in the huntingtin (HTT) protein. A number of differentially-expressed protein molecules have been identified in striatum of HD animal models. Here we examined if the expression changes could be visualized in the peripheral leukocytes of HD patients and pre-symptomatic HD (PreHD) carriers.Methods and findingsThe expression levels of 17 candidate genes that differentially expressed in striatum between transgenic HD and wild-type mice in literature were measured in the peripheral leukocytes of 4 PreHD carriers, 16 HD patients and 20 healthy controls. Four genes majorly involved in metabolism and oxidative stress response, including AHCY1, ACO2, OXCT1 and CAP1, demonstrated consistent downregulation in peripheral leukocytes of both PreHD carriers and HD patients, while UCP2 was only down-regulated in HD patients.ConclusionThese results provide potential peripheral biomarkers to indicate disease onset in preclinical stage, and to monitor the efficacy of early treatment. Further studies of a large series of preHD carriers and symptomatic HD patients will be warranted to verify the findings and examine if these markers correlate with clinical features.

show abstract

“…The therapeutic strategy reduces the reactive oxygen radicals might improve the neurodegeneration process by using CoQ10 which acts as antioxidants. (25).…”

Section: Parkinson's Disease (Pd)mentioning

confidence: 99%

A review of the effect of Coenzyme Q10 in patients with polycystic ovary syndrome

Badr¹,

Althanoon²

2021

Iraqi J. Pharm.

View full text Add to dashboard Cite

Background: Women with polycystic ovary syndrome are usually suffering from many metabolic disturbances as insulin resistance, so the use of Co enzyme Q10 in those patients improve metabolic changes and insulin resistance resulting in better ovulation. Mitochondrial dysfunction in the eggs is related to reduction in the oxidative phosphorylation which leads to lower ATP production by mitochondria, also results in deprived reproductive performance, including poor oocyte quality, lessened ovarian store, abnormal conception and unbalanced embryo development.Objective: The aim of this review is to observe the effects of co enzyme Q10 in PCOS patients by emphasizing many studies that showing the effect of CoQ10 on the metabolic parameters such as (Fasting serum glucose, HbA1c%, total cholesterol, LDL, HDL and triglyceride level). This article suggested that CoQ10 therapy possess beneficial effect in improving the clinical parameters of PCOS patients including HbA1c%, fasting serum glucose and lipid profile parameters.

show abstract

Mitochondrial and metabolic-based protective strategies in Huntington’s disease: the case of creatine and coenzyme Q

Cited by 18 publications

References 187 publications

Activation of IGF-1 and Insulin Signaling Pathways Ameliorate Mitochondrial Function and Energy Metabolism in Huntington’s Disease Human Lymphoblasts

Activation of IGF-1 and Insulin Signaling Pathways Ameliorate Mitochondrial Function and Energy Metabolism in Huntington’s Disease Human Lymphoblasts

Downregulation of Genes Involved in Metabolism and Oxidative Stress in the Peripheral Leukocytes of Huntington's Disease Patients

A review of the effect of Coenzyme Q10 in patients with polycystic ovary syndrome

Contact Info

Product

Resources

About