Abstract
Alzheimers disease (AD), the leading cause of senile dementia, has become a considerable social and economical problem. Current AD therapeutics provide mainly symptomatic short-term benefit, rather than targeting disease mechanisms. The hallmarks for AD are ß-amyloid plaques, neurofibrillary tangles, and regionalized neuronal loss. Additional neuropathological features have been described that may provide some clues to the mechanism by which neurons die in AD. Specifically, the aberrant expression of cell cycle proteins and the presence of de novo-replicated DNA in neurons have been described both in AD brain and in culture models of the disease. The unscheduled cell cycle events are deleterious to neurons, which undergo death rather than complete the cell cycle. Although our understanding of the neuronal cell cycle is not complete, experimental evidence suggests that compounds able of arresting the aberrant cell cycle will yield neuroprotection. This review focuses on drug development centered on the cell cycle hypothesis of AD.
Keywords: Alzheimer's disease, β-amyloid, apoptosis, cell cycle, DNA replication, cyclin-dependent kinases, DNA polymerase-β, neuroprotection
Current Medicinal Chemistry
Title: The Cell Cycle Molecules Behind Neurodegeneration in Alzheimers Disease: Perspectives for Drug Development
Volume: 15 Issue: 24
Author(s): A. Copani, S. Guccione, L. Giurato, F. Caraci, M. Calafiore, M. A. Sortino and F. Nicoletti
Affiliation:
Keywords: Alzheimer's disease, β-amyloid, apoptosis, cell cycle, DNA replication, cyclin-dependent kinases, DNA polymerase-β, neuroprotection
Abstract: Alzheimers disease (AD), the leading cause of senile dementia, has become a considerable social and economical problem. Current AD therapeutics provide mainly symptomatic short-term benefit, rather than targeting disease mechanisms. The hallmarks for AD are ß-amyloid plaques, neurofibrillary tangles, and regionalized neuronal loss. Additional neuropathological features have been described that may provide some clues to the mechanism by which neurons die in AD. Specifically, the aberrant expression of cell cycle proteins and the presence of de novo-replicated DNA in neurons have been described both in AD brain and in culture models of the disease. The unscheduled cell cycle events are deleterious to neurons, which undergo death rather than complete the cell cycle. Although our understanding of the neuronal cell cycle is not complete, experimental evidence suggests that compounds able of arresting the aberrant cell cycle will yield neuroprotection. This review focuses on drug development centered on the cell cycle hypothesis of AD.
Export Options
About this article
Cite this article as:
Copani A., Guccione S., Giurato L., Caraci F., Calafiore M., Sortino A. M. and Nicoletti F., The Cell Cycle Molecules Behind Neurodegeneration in Alzheimers Disease: Perspectives for Drug Development, Current Medicinal Chemistry 2008; 15 (24) . https://dx.doi.org/10.2174/092986708785909030
DOI https://dx.doi.org/10.2174/092986708785909030 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |

- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
- Announcements
Related Articles
-
Modulation of Retinal Arteriolar Central Reflection by APOE Genotype
Current Alzheimer Research Editorial [ Hot Topic: Anti Alzheimer Agents (Guest Editor: Helmut Hugel)]
Mini-Reviews in Medicinal Chemistry Selective Modulators of α<sub>5</sub>-Containing GABA<sub>A</sub> Receptors and their Therapeutic Significance
Current Drug Targets Polyphenols: A Potential New Strategy for the Prevention and Treatment of Anxiety and Depression
Current Nutrition & Food Science Central Nervous System Acting Drugs in Treatment of Migraine Headache
Central Nervous System Agents in Medicinal Chemistry Conference Report: 182nd AAAS Annual Meeting, Washington DC, February 11-15, 2016
CNS & Neurological Disorders - Drug Targets Receptor for AGEs (RAGE) as Mediator of NF-kB Pathway Activation in Neuroinflammation and Oxidative Stress
CNS & Neurological Disorders - Drug Targets Molecular Basis of Familial and Sporadic Alzheimer's Disease
Current Alzheimer Research Isolation and Characterisation of Acetylcholinesterase Inhibitors from Aquilaria subintegra for the Treatment of Alzheimer’s Disease (AD)
Current Alzheimer Research Structure – Function Relationships of Pre-Fibrillar Protein Assemblies in Alzheimers Disease and Related Disorders
Current Alzheimer Research The Role of VE-cadherin in Blood-brain Barrier Integrity Under Central Nervous System Pathological Conditions
Current Neuropharmacology New Developments of Clinical Trial in Immunotherapy for Alzheimer's Disease
Current Pharmaceutical Biotechnology Towards Newer Molecular Targets for Chronic Diabetic Complications
Current Vascular Pharmacology Molecular Pathways Involved in Apoptotic Cell Death in the Injured Cochlea: Cues to Novel Therapeutic Strategies
Current Pharmaceutical Design Potential Role of Polyphenols in the Prevention of Cardiovascular Diseases: Molecular Bases
Current Medicinal Chemistry Biomarker Positive and Negative Subjects in the ADNI Cohort: Clinical Characterization
Current Alzheimer Research Editorial from Guest Editor [Hot topic: Community-Acquired Pneumonia – Evolving Changes in Our Understanding and How This Impacts on Management (Guest Editor: Grant Waterer)]
Current Respiratory Medicine Reviews Therapeutic Perspectives in Alzheimers Disease
Recent Patents on CNS Drug Discovery (Discontinued) Total Bakkenolides Protects Neurons Against Cerebral Ischemic Injury Through Inhibition of Nuclear Factor-κB Activation
CNS & Neurological Disorders - Drug Targets Role of CNS Transporters in the Pharmacotherapy of HIV-1 Associated Neurological Disorders
Current Pharmaceutical Design