Abstract
In Alzheimer's disease and Down syndrome, cholinergic neurons of the basal forebrain progressively degenerate. This neurotransmitter system is the main source of acetylcholine to the cortex and hippocampus. In the mature and fully differentiated central nervous system, the phenotype of forebrain cholinergic neurons and their nerve terminals in cortex and hippocampus depend on the continuous endogenous supply of nerve growth factor (NGF). It has been recently demonstrated that NGF is secreted from cortical neurons in an activity-dependent manner as a precursor molecule, proNGF. Individuals with Alzheimer’s disease and Down syndrome exhibit proNGF accumulation in cortex, yet cholinergic neurons become atrophic in both diseases, despite the apparent abundance of the NGF precursor. This review illustrates the recent evidence that NGF metabolism is affected both in Alzheimer’s disease and in Down syndrome brains and also discusses a role for amyloid-β peptides and central nervous system inflammation in unleashing such deficits. It further considers the potential of the NGF metabolic pathway as a new pharmacological target to slow down the neurodegenerative process both in Alzheimer’s disease and in individuals with Down syndrome.
Keywords: Alzheimer’s disease, cholinergic neurons, Down syndrome, inflammation, metallo-proteases, nerve growth factor, nerve growth factor metabolism.
CNS & Neurological Disorders - Drug Targets
Title:A Link Between Nerve Growth Factor Metabolic Deregulation and Amyloid-β-Driven Inflammation in Down Syndrome
Volume: 15 Issue: 4
Author(s): Maria Florencia Iulita, Filippo Caraci and Augusto Claudio Cuello
Affiliation:
Keywords: Alzheimer’s disease, cholinergic neurons, Down syndrome, inflammation, metallo-proteases, nerve growth factor, nerve growth factor metabolism.
Abstract: In Alzheimer's disease and Down syndrome, cholinergic neurons of the basal forebrain progressively degenerate. This neurotransmitter system is the main source of acetylcholine to the cortex and hippocampus. In the mature and fully differentiated central nervous system, the phenotype of forebrain cholinergic neurons and their nerve terminals in cortex and hippocampus depend on the continuous endogenous supply of nerve growth factor (NGF). It has been recently demonstrated that NGF is secreted from cortical neurons in an activity-dependent manner as a precursor molecule, proNGF. Individuals with Alzheimer’s disease and Down syndrome exhibit proNGF accumulation in cortex, yet cholinergic neurons become atrophic in both diseases, despite the apparent abundance of the NGF precursor. This review illustrates the recent evidence that NGF metabolism is affected both in Alzheimer’s disease and in Down syndrome brains and also discusses a role for amyloid-β peptides and central nervous system inflammation in unleashing such deficits. It further considers the potential of the NGF metabolic pathway as a new pharmacological target to slow down the neurodegenerative process both in Alzheimer’s disease and in individuals with Down syndrome.
Export Options
About this article
Cite this article as:
Iulita Florencia Maria, Caraci Filippo and Cuello Claudio Augusto, A Link Between Nerve Growth Factor Metabolic Deregulation and Amyloid-β-Driven Inflammation in Down Syndrome, CNS & Neurological Disorders - Drug Targets 2016; 15 (4) . https://dx.doi.org/10.2174/1871527315666160321104916
DOI https://dx.doi.org/10.2174/1871527315666160321104916 |
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
-
Safety Considerations Associated with Development and Clinical Application of Lentiviral Vector Systems for Gene Transfer
Current Genomics Targeting the Oncogenic Tyrosine Kinase NPM-ALK in Lymphoma: The Role of Murine Models in Defining Pathogenesis and Treatment Options
Current Drug Targets Platelet Activity in the Pathophysiology of Inflammatory Bowel Diseases
Current Drug Targets Effects of Drug Transporters on Pharmacological Responses and Safety
Current Drug Metabolism Targeting the BH3 Domain of Bcl-2 Family Proteins. A Brief History From Natural Products to Foldamers As Promising Cancer Therapeutic Avenues
Current Medicinal Chemistry The Role and Therapeutic Potential of Ser/Thr Phosphatase PP2A in Apoptotic Signalling Networks in Human Cancer Cells
Current Molecular Medicine Recent Advances in Heterocyclic Tubulin Inhibitors Targeting the Colchicine Binding Site
Anti-Cancer Agents in Medicinal Chemistry Fetuin-A: A Multifunctional Protein
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery ARC - Augmented Renal Clearance
Current Pharmaceutical Biotechnology Technetium Labeled Small Peptide Radiopharmaceuticals in the Identification of Lung Cancer
Current Pharmaceutical Design Tubulin Maytansine Site Binding Ligands and their Applications as MTAs and ADCs for Cancer Therapy
Current Medicinal Chemistry Development of Fourth Generation ABC Inhibitors from Natural Products: A Novel Approach to Overcome Cancer Multidrug Resistance
Anti-Cancer Agents in Medicinal Chemistry Human Equilibrative Nucleoside Transporter 1 (hENT1) Levels Predict Response to Gemcitabine in Patients With Biliary Tract Cancer (BTC)
Current Cancer Drug Targets The Changing Face of HDAC Inhibitor Depsipeptide
Current Cancer Drug Targets Methotrexate-Induced Pneumonitis: Heterogeneity of Bronchoalveolar Lavage and Differences between Cancer and Rheumatoid Arthritis
Inflammation & Allergy - Drug Targets (Discontinued) Novel Mechanisms of Anticancer Activities of Green Tea Component Epigallocatechin- 3-Gallate
Anti-Cancer Agents in Medicinal Chemistry Antiangiogenic Therapy
Current Pharmaceutical Design microRNA, Cancer and Cancer Chemoprevention
Current Molecular Pharmacology Bypassing Cancer Resistance by Antagonizing “Inhibitor of Apoptosis Proteins” (IAPs)
Current Signal Transduction Therapy Molecular Pathways Linking Inflammation and Cancer
Current Molecular Medicine