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
- 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
-
Highly Active Antiretroviral Therapy and Cardiovascular Complications in HIV-Infected Patients
Current Pharmaceutical Design New Approaches for the Treatment of Mental Disorders Comorbid with Inflammatory Diseases
Current Topics in Medicinal Chemistry LRRK2 Kinase Inhibition as a Therapeutic Strategy for Parkinson’s Disease, Where Do We Stand?
Current Neuropharmacology The GABA Shunt: An Attractive and Potential Therapeutic Target in the Treatment of Epileptic Disorders
Current Drug Metabolism Combined Therapies for Lysosomal Storage Diseases
Current Molecular Medicine Brain Network Connectivity Mediates Education-related Cognitive Performance in Healthy Elderly Adults
Current Alzheimer Research Recent Developments in Natural and Synthetic Drug Research for Alzheimers Disease
Letters in Drug Design & Discovery The Central Vasopressinergic System: Examining the Opportunities for Psychiatric Drug Development
Current Pharmaceutical Design The Multifactorial Nature of Alzheimer's Disease for Developing Potential Therapeutics
Current Topics in Medicinal Chemistry Tau-Focused Immunotherapy for Alzheimers Disease and Related Tauopathies
Current Alzheimer Research Neuropsychiatric and Cognitive Symptoms in Spinocerebellar Ataxia: Relationship to Neuropathological Differences
Current Psychiatry Reviews New Therapeutic Strategy for Parkinson’s and Alzheimer’s Disease
Current Medicinal Chemistry Autophagy Modulators and Neuroinflammation
Current Medicinal Chemistry Oxidative Stress Induced Mitochondrial DNA Deletion as a Hallmark forthe Drug Development in the Context of the Cerebrovascular Diseases
Recent Patents on Cardiovascular Drug Discovery Editorial [ Hot Topic: Anti Alzheimer Agents (Guest Editor: Helmut Hugel)]
Mini-Reviews in Medicinal Chemistry Brain Derived Neurotrophic Factor and Cognitive Status: The Delicate Balance Among People Living with HIV, with and without Alcohol Abuse
Current HIV Research NOAC in Acute Coronary Syndrome and AF?
Cardiovascular & Hematological Disorders-Drug Targets Current Nervous System Related Drug Targets for the Treatment of Amyotrophic Lateral Sclerosis
Current Pharmaceutical Design The Use of Proteomics to Study Infectious Diseases
Infectious Disorders - Drug Targets Cerebrovascular Complications of Diabetes: SGLT-2 Inhibitors as a Promising Future Therapeutics
Current Drug Targets