Abstract
There are myriads of reasons and ways for a neuron to die, among which apoptosis is a specific form that is processed in two major signaling pathways, the TNF-receptor-mediated (extrinsic) and the mitochondria-based (intrinsic) cell death pathway with several avenues of crosstalk between them. The molecular key players of apoptosis, the importance of the Csp cascade via interaction with different death effector domains and the role of the effector Csp-3 driving the execution of the cell death program are reviewed. Recent data suggest that caspases converge amyloid and tau Alzheimer pathologies: β amyloid peptide activates caspases which on turn cleave tau and via phosphorylation of tau initiate tangle pathology in both Alzheimer disease and other tauopathies. Several mediators show a bifunctional regulation of apoptosis, with both pro- and anti-apoptotic activities. The latter modify the cell death pathway due to inhibition of Csp activation or other protective mechanisms and may delay it or, via abortive apoptosis ("abortosis") lead to prolonged survival of nerve cells. While the role of apoptosis in neurodegeneration is well documented in tissue culture and transgenic animal models, in human postmorten AD brain its occurrence and role are discussed controversially. Given the short duration required for the completion of apoptosis and the chronic progressive course of neurodegeneration in Alzheimer disease and related disorders, the detection of rare neurons displaying morphological signs of apoptosis and expression of the activated keyexecuting enzyme Csp-3 is realistic, although there is significantly increased incidence of cells with DNA fragmentaion, mainly glia, and markers for a "proapoptotic" environment in the aged human brain indicate increased susceptibility of neurons to metabolic and other noxious factors. Postmortem analysis can bridge some but not all of our knowledge gaps, but the results are still controversial, and we need a better understanding of the molecular basis and pathways that drive the yin-yang between neuronal survival and death.
Keywords: Apoptosis, programmed cell death, signaling pathways, caspases, death effector domain, cell cycle, β amyloid protein, tau phosphorylation, Alzheimer disease
Current Alzheimer Research
Title: Challenges in Neuronal Apoptosis
Volume: 3 Issue: 4
Author(s): Kurt A. Jellinger
Affiliation:
Keywords: Apoptosis, programmed cell death, signaling pathways, caspases, death effector domain, cell cycle, β amyloid protein, tau phosphorylation, Alzheimer disease
Abstract: There are myriads of reasons and ways for a neuron to die, among which apoptosis is a specific form that is processed in two major signaling pathways, the TNF-receptor-mediated (extrinsic) and the mitochondria-based (intrinsic) cell death pathway with several avenues of crosstalk between them. The molecular key players of apoptosis, the importance of the Csp cascade via interaction with different death effector domains and the role of the effector Csp-3 driving the execution of the cell death program are reviewed. Recent data suggest that caspases converge amyloid and tau Alzheimer pathologies: β amyloid peptide activates caspases which on turn cleave tau and via phosphorylation of tau initiate tangle pathology in both Alzheimer disease and other tauopathies. Several mediators show a bifunctional regulation of apoptosis, with both pro- and anti-apoptotic activities. The latter modify the cell death pathway due to inhibition of Csp activation or other protective mechanisms and may delay it or, via abortive apoptosis ("abortosis") lead to prolonged survival of nerve cells. While the role of apoptosis in neurodegeneration is well documented in tissue culture and transgenic animal models, in human postmorten AD brain its occurrence and role are discussed controversially. Given the short duration required for the completion of apoptosis and the chronic progressive course of neurodegeneration in Alzheimer disease and related disorders, the detection of rare neurons displaying morphological signs of apoptosis and expression of the activated keyexecuting enzyme Csp-3 is realistic, although there is significantly increased incidence of cells with DNA fragmentaion, mainly glia, and markers for a "proapoptotic" environment in the aged human brain indicate increased susceptibility of neurons to metabolic and other noxious factors. Postmortem analysis can bridge some but not all of our knowledge gaps, but the results are still controversial, and we need a better understanding of the molecular basis and pathways that drive the yin-yang between neuronal survival and death.
Export Options
About this article
Cite this article as:
Jellinger A. Kurt, Challenges in Neuronal Apoptosis, Current Alzheimer Research 2006; 3 (4) . https://dx.doi.org/10.2174/156720506778249434
DOI https://dx.doi.org/10.2174/156720506778249434 |
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
Alzheimer's Disease Drug Development
Alzheimer's disease is a progressive neurodegenerative disorder that affects millions of people worldwide. Despite decades of research, no cure or disease-modifying treatment is available yet. Therefore, the need for developing effective therapies to treat Alzheimer's disease is an urgent matter. This special issue aims to provide a comprehensive overview of ...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
![](/images/wayfinder.jpg)
- 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
-
Modulation of Ion Channels in Pulmonary Arterial Hypertension
Current Pharmaceutical Design Chalcone Derivatives Activate and Desensitize the Transient Receptor Potential Ankyrin 1 Cation Channel, Subfamily A, Member 1 TRPA1 Ion Channel: Structure-Activity Relationships in vitro and Anti-Nociceptive and Anti-inflammatory Activity in vivo
CNS & Neurological Disorders - Drug Targets Melatonin: Pharmacology, Functions and Therapeutic Benefits
Current Neuropharmacology Toward a Developmentally Centered Approach to Adolescent Alcohol and Substance Use Treatment
Current Drug Abuse Reviews Aberrant Splicing, Hyaluronan Synthases and Intracellular Hyaluronan as Drivers of Oncogenesis and Potential Drug Targets
Current Cancer Drug Targets Artificial Anion Transporters in Bilayer Membranes
Current Drug Discovery Technologies Pantothenate Kinase-Associated Neurodegeneration
Current Drug Targets Effects of an Acute Treatment with L-Thyroxine on Memory, Habituation, Danger Avoidance, and on Na+, K+-ATPase activity in Rat Brain
Current Neurovascular Research The Enigmatic Drug Binding Site for Sodium Channel Inhibitors
Current Molecular Pharmacology On the Analysis of Fingertip Photoplethysmogram Signals
Current Cardiology Reviews Preoperative Functional Magnetic Resonance Imaging (fMRI) and Transcranial Magnetic Stimulation (TMS)
Current Medical Imaging Psychological and Mental Health Issues During the SARS-CoV-2 Global Pandemic: A Critical Analysis
Coronaviruses Polyphenols Beyond Barriers: A Glimpse into the Brain
Current Neuropharmacology Vital Elements of the Wnt-Frizzled Signaling Pathway in the Nervous System
Current Neurovascular Research Hereditary Heterozygous C2 Deficiency: Variable Clinical and Serological Manifestations Among Three Sisters
Current Rheumatology Reviews Pain-Related Behavior and Brain Activation in a Cynomolgus Macaque Model of Postoperative Pain
CNS & Neurological Disorders - Drug Targets Emerging Risk Factors for Cerebrovascular Disease
Current Drug Targets Biochemical and Structural Investigations on Kynurenine Aminotransferase II: An Example of Conformation-Driven Species-Specific Inhibition?
Current Topics in Medicinal Chemistry Targeting Polymeric Nanobiomaterials as a Platform for Cartilage Tissue Engineering
Current Pharmaceutical Design Diabetic Retinopathy: Current and New Treatment Options
Current Diabetes Reviews