Abstract
Synaptic degeneration and death of neurons in limbic and cortical brain regions are the fundamental processes responsible for the manifestation of cognitive dysfunction and behavioural abnormalities in Alzheimers disease (AD). Despite the various genetic and environmental factors, and the aging process itself that may lead to the manifestation of AD, multiple evidence from studies in experimental models and in AD brain tissue demonstrate that the underlying neurodegeneration is associated with morphological and biochemical features of apoptosis. At the cellular level, neuronal apoptosis in AD may be initiated by oxidative stress and related DNA damage, disruption of cellular calcium homeostasis, or endoplasmic reticulum (ER) stress. The molecular mechanisms of the biochemical cascades of apoptosis are beginning to be understood and involve upstream effectors such as Par-4, p53, and pro-apoptotic Bcl-2 family members, which mediate mitochondrial dysfunction and subsequent release of pro-apoptotic proteins, such as cytochrome c or apoptosis inducing factor (AIF), and subsequent caspase-dependent and -independent pathways which finally result in degradation of proteins and nuclear DNA. The regulation of apoptotic cascades is complex and involves transcriptional control as well as posttranscriptional protein modifications, such as protease-mediated cleavage, ubiquitination or poly(ADP-ribosylation). More recently, the regulation of protein phosphorylation by kinases and phosphatases is emerging as a prerequisite mechanism in the control of the apoptotic cell death program. A better understanding of the molecular underpinnings of neuronal apoptosis will lead to novel preventive and therapeutic approaches to the neurodegenerative processes in Alzheimers disease and other neurological disorders where programmed cell death is prominent.
Keywords: Alzheimer's disease, oxidative stress, DNA damage, ER stress, Par-4, AIF, GSK-3β, protein phosphatases
Current Alzheimer Research
Title: Molecular Insights into Mechanisms of the Cell Death Program:Role in the Progression of Neurodegenerative Disorders
Volume: 3 Issue: 4
Author(s): Carsten Culmsee and Stefan Landshamer
Affiliation:
Keywords: Alzheimer's disease, oxidative stress, DNA damage, ER stress, Par-4, AIF, GSK-3β, protein phosphatases
Abstract: Synaptic degeneration and death of neurons in limbic and cortical brain regions are the fundamental processes responsible for the manifestation of cognitive dysfunction and behavioural abnormalities in Alzheimers disease (AD). Despite the various genetic and environmental factors, and the aging process itself that may lead to the manifestation of AD, multiple evidence from studies in experimental models and in AD brain tissue demonstrate that the underlying neurodegeneration is associated with morphological and biochemical features of apoptosis. At the cellular level, neuronal apoptosis in AD may be initiated by oxidative stress and related DNA damage, disruption of cellular calcium homeostasis, or endoplasmic reticulum (ER) stress. The molecular mechanisms of the biochemical cascades of apoptosis are beginning to be understood and involve upstream effectors such as Par-4, p53, and pro-apoptotic Bcl-2 family members, which mediate mitochondrial dysfunction and subsequent release of pro-apoptotic proteins, such as cytochrome c or apoptosis inducing factor (AIF), and subsequent caspase-dependent and -independent pathways which finally result in degradation of proteins and nuclear DNA. The regulation of apoptotic cascades is complex and involves transcriptional control as well as posttranscriptional protein modifications, such as protease-mediated cleavage, ubiquitination or poly(ADP-ribosylation). More recently, the regulation of protein phosphorylation by kinases and phosphatases is emerging as a prerequisite mechanism in the control of the apoptotic cell death program. A better understanding of the molecular underpinnings of neuronal apoptosis will lead to novel preventive and therapeutic approaches to the neurodegenerative processes in Alzheimers disease and other neurological disorders where programmed cell death is prominent.
Export Options
About this article
Cite this article as:
Culmsee Carsten and Landshamer Stefan, Molecular Insights into Mechanisms of the Cell Death Program:Role in the Progression of Neurodegenerative Disorders, Current Alzheimer Research 2006; 3 (4) . https://dx.doi.org/10.2174/156720506778249461
DOI https://dx.doi.org/10.2174/156720506778249461 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...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
- Announcements
Related Articles
-
New Insights into the Roles of Endolysosomal Cathepsins in the Pathogenesis of Alzheimers Disease: Cathepsin Inhibitors as Potential Therapeutics
CNS & Neurological Disorders - Drug Targets Editorial: [Hot Topic: Therapeutic Antioxidants for Neurodegenerative Disease]
Recent Patents on CNS Drug Discovery (Discontinued) NAP (Davunetide) Provides Functional and Structural Neuroprotection
Current Pharmaceutical Design Effect of Trichostatin A on Gelsolin Levels, Proteolysis of Amyloid Precursor Protein, and Amyloid Beta-Protein Load in the Brain of Transgenic Mouse Model of Alzheimer's Disease
Current Alzheimer Research 9th International Meeting on Metabotropic Gglutamate Receptors (Taormina, Sicily, October 1-6, 2017).
Current Neuropharmacology Neuronal Cell Death in Alzheimers Disease and a Neuroprotective Factor, Humanin
Current Neuropharmacology Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Other Anti- Inflammatory Agents in the Treatment of Neurodegenerative Disease
Current Alzheimer Research Mitophagy in Neurodegeneration: An Opportunity for Therapy?
Current Drug Targets Life and Death of Nerve Cells: Therapeutic Cytokine Signaling Pathways
Current Signal Transduction Therapy Combating Protein Misfolding and Aggregation by Intracellular Antibodies
Current Molecular Medicine The Emerging Role of the Cannabinoid Receptor Family in Peripheral and Neuro-immune Interactions
Current Drug Targets Receptor for AGEs (RAGE) as Mediator of NF-kB Pathway Activation in Neuroinflammation and Oxidative Stress
CNS & Neurological Disorders - Drug Targets The Potential Role of Glycogen Synthase Kinase 3 Inhibitors as Amyotrophic Lateral Sclerosis Pharmacological Therapy
Current Medicinal Chemistry Current Challenges to Overcome in the Management of Type 2 Diabetes Mellitus and Associated Neurological Disorders
CNS & Neurological Disorders - Drug Targets Computational Biology of Olfactory Receptors
Current Bioinformatics Protective Effects of Pomegranate in Endothelial Dysfunction
Current Pharmaceutical Design The Role of IRE1 Signaling in the Central Nervous System Diseases
Current Neuropharmacology Neurotransmitters and Microglial-Mediated Neuroinflammation
Current Protein & Peptide Science Therapeutic Potential of Vasoactive Intestinal Peptide and its Receptors in Neurological Disorders
CNS & Neurological Disorders - Drug Targets Sirtuins: Developing Innovative Treatments for Aged-Related Memory Loss and Alzheimer’s Disease
Current Neurovascular Research