ArticleMolecular neurobiology2015
Activation of IGF-1 and insulin signaling pathways ameliorate mitochondrial function and energy metabolism in Huntington's Disease human lymphoblasts.
Article in Molecular neurobiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 76 citations in OpenAlex.
- Insulin-like growth factor receptor signaling in physiology and disease.Signal transduction and targeted therapy · 2026Review
- DNA methylation profiling in Huntington's disease reveals disease associated changes in the striatum.Clinical epigenetics · 2026Article
- IGF1R deficiency mitigates acute lung injury by promoting anti-inflammatory transcriptional profiles.Respiratory research · 2025Article
- The Role of MicroRNAs in Neurodegeneration: Insights from Huntington's Disease.Molecular neurobiology · 2025Review
- Growth Factors and Their Application in the Therapy of Hereditary Neurodegenerative Diseases.Biomedicines · 2024Review
- Renin-angiotensin system inhibitors positively impact on multiple aging regulatory pathways: Could they be used to protect against human aging?Physiological reports · 2024Review
- Exploring molecular mechanisms, therapeutic strategies, and clinical manifestations of Huntington's disease.Archives of pharmacal research · 2024Review
- Association Between Insulin-Like Growth Factor-1 and Social Cognition in Huntington's Disease.Movement disorders clinical practice · 2023Article
- Interactions of amyloidogenic proteins with mitochondrial protein import machinery in aging-related neurodegenerative diseases.Frontiers in physiology · 2023Review
- Integrative Profiling of Amyotrophic Lateral Sclerosis Lymphoblasts Identifies Unique Metabolic and Mitochondrial Disease Fingerprints.Molecular neurobiology · 2022Article
- Activation of IGF-1/GLP-1 Signalling via 4-Hydroxyisoleucine Prevents Motor Neuron Impairments in Experimental ALS-Rats Exposed to Methylmercury-Induced Neurotoxicity.Molecules (Basel, Switzerland) · 2022Article
- Analysis of Mitochondrial Dysfunction by Microplate Reader in hiPSC-Derived Neuronal Cell Models of Neurodegenerative Disorders.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Macroautophagy and Mitophagy in Neurodegenerative Disorders: Focus on Therapeutic Interventions.Biomedicines · 2021Review
- New Avenues for the Treatment of Huntington's Disease.International journal of molecular sciences · 2021Review
- Neonatal Rotenone Administration Induces Psychiatric Disorder-Like Behavior and Changes in Mitochondrial Biogenesis and Synaptic Proteins in Adulthood.Molecular neurobiology · 2021Article
- Lymphoblastoid Cell Lines as Models to Study Mitochondrial Function in Neurological Disorders.International journal of molecular sciences · 2021Review
- Mutant HTT (huntingtin) impairs mitophagy in a cellular model of Huntington disease.Autophagy · 2021Article
- IGF1R Deficiency Modulates Brain Signaling Pathways and Disturbs Mitochondria and Redox Homeostasis.Biomedicines · 2021Article
- Oxygen Consumption Evaluation: An Important Indicator of Metabolic State, Cellular Function, and Cell Fate Along Neural Deregulation.Methods in molecular biology (Clifton, N.J.) · 2021Article
- A Balanced Act: The Effects of GH-GHR-IGF1 Axis on Mitochondrial Function.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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