Abstract
An increasing amount of evidence suggests that the dysregulation of the Akt-mTOR (Akt-mammalian Target Of Rapamycin) signaling network is associated with intellectual disabilities, such as fragile X, tuberous sclerosis and Rett’s syndrome. The Akt-mTOR pathway is involved in dendrite morphogenesis and synaptic plasticity, and it has been shown to modulate both glutamatergic and GABAergic synaptic transmission. We have recently shown that the AktmTOR pathway is hyperactive in the hippocampus of Ts1Cje mice, a model of Down’s syndrome, leading to increased local dendritic translation that could interfere with synaptic plasticity. Rapamycin and rapalogs are specific inhibitors of mTOR, and some of these inhibitors are Food and Drug Administration-approved drugs. In this review, we discuss the molecular basis and consequences of Akt-mTOR hyperactivation in Down’s syndrome, paying close attention to alterations in the molecular mechanisms underlying synaptic plasticity. We also analyze the pros and cons of using rapamycin/rapalogs for the treatment of the cognitive impairments associated with this condition.
Keywords: Akt, Brain-Derived Neurotrophic Factor, Down’s syndrome, local translation, mammalian Target of Rapamycin, rapamycin, trisomy 21, Ts1Cje.
CNS & Neurological Disorders - Drug Targets
Title:The Akt-mTOR Pathway in Down’s Syndrome: The Potential Use of Rapamycin/Rapalogs for Treating Cognitive Deficits
Volume: 13 Issue: 1
Author(s): Jose Antonio Troca-Marin, Juan Jose Casanas, Itziar Benito and Maria Luz Montesinos
Affiliation:
Keywords: Akt, Brain-Derived Neurotrophic Factor, Down’s syndrome, local translation, mammalian Target of Rapamycin, rapamycin, trisomy 21, Ts1Cje.
Abstract: An increasing amount of evidence suggests that the dysregulation of the Akt-mTOR (Akt-mammalian Target Of Rapamycin) signaling network is associated with intellectual disabilities, such as fragile X, tuberous sclerosis and Rett’s syndrome. The Akt-mTOR pathway is involved in dendrite morphogenesis and synaptic plasticity, and it has been shown to modulate both glutamatergic and GABAergic synaptic transmission. We have recently shown that the AktmTOR pathway is hyperactive in the hippocampus of Ts1Cje mice, a model of Down’s syndrome, leading to increased local dendritic translation that could interfere with synaptic plasticity. Rapamycin and rapalogs are specific inhibitors of mTOR, and some of these inhibitors are Food and Drug Administration-approved drugs. In this review, we discuss the molecular basis and consequences of Akt-mTOR hyperactivation in Down’s syndrome, paying close attention to alterations in the molecular mechanisms underlying synaptic plasticity. We also analyze the pros and cons of using rapamycin/rapalogs for the treatment of the cognitive impairments associated with this condition.
Export Options
About this article
Cite this article as:
Troca-Marin Antonio Jose, Casanas Jose Juan, Benito Itziar and Montesinos Luz Maria, The Akt-mTOR Pathway in Down’s Syndrome: The Potential Use of Rapamycin/Rapalogs for Treating Cognitive Deficits, CNS & Neurological Disorders - Drug Targets 2014; 13 (1) . https://dx.doi.org/10.2174/18715273113126660184
DOI https://dx.doi.org/10.2174/18715273113126660184 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Recent Progress on Apoptotic Activity of Triazoles
Current Drug Targets DAB389EGF Fusion Protein Therapy of Refractory Glioblastoma Multiforme
Current Pharmaceutical Biotechnology The Use of Cytokines and Chemokines in the Cancer Immunotherapy
Recent Patents on Anti-Cancer Drug Discovery Bortezomib in the Treatment of Cancer
Recent Patents on Anti-Cancer Drug Discovery Mitochondrial-Targeted Plastoquinone Derivatives. Effect on Senescence and Acute Age-Related Pathologies
Current Drug Targets SAR, QSAR and Docking of Anticancer Flavonoids and Variants: A Review
Current Topics in Medicinal Chemistry The Discovery of the Potent and Selective Antitumour Agent 2-(4-Amino-3-methylphenyl)benzothiazole (DF 203) and Related Compounds
Current Medicinal Chemistry Nutrition and NSCLC; Should We Administer Food Supplements?
Current Pharmaceutical Design miR-15b and miR-21 as Circulating Biomarkers for Diagnosis of Glioma
Current Genomics The Role of Chromogranin A (CgA) in Monitoring Patients with Prostate Cancer Under Androgen Deprivation Therapy: Comparison with Prostatic Specific Antigen (PSA)
Current Radiopharmaceuticals Thromboembolic Complications in Malignant Haematological Disorders
Current Vascular Pharmacology Emerging Drug Target In Pancreatic Cancer: Placing Sirtuin 1 on the Canvas
Current Cancer Drug Targets Post-Translational Control of Sp-Family Transcription Factors
Current Genomics Titanocene Y and Vanadocene Y: Platinum Resistance-Breaking Cytotoxic and DNA-Targeting Anticancer Drug Candidates
Letters in Drug Design & Discovery Disease-Related Changes in TRPV1 Expression and Its Implications for Drug Development
Current Topics in Medicinal Chemistry Alzheimer’s Disease and Antioxidant Therapy: How Long How Far?
Current Medicinal Chemistry Interrelationships with Metabolic Syndrome, Obesity and Cardiovascular Risk
Current Vascular Pharmacology The Anticancer Face of Interferon Alpha (IFN-Alpha): From Biology to Clinical Results, with a Focus on Melanoma
Current Medicinal Chemistry Inflammatory Mediators Hold the Key to Dendritic Cell Suppression and Tumor Progression
Current Medicinal Chemistry Cellular Players in Lung Fibrosis
Current Pharmaceutical Design