![conference banner](/images/conference-banner.jpeg)
Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder caused by loss of motor neurons both in the brain and spinal cord, which dramatically reduces life expectancy. ALS occurs either in familial ALS or, more frequently, in sporadic ALS forms. Several mechanisms have been postulated to underlie motor neuron death. In the present paper, starting from some of the genes related to familial ALS, we overview and discuss their potential role in modifying of the physiological clearance of altered proteins and organelles in motor neurons. Special emphasis is placed on the role of autophagy, which seems to prevail as a protein clearing system over other multienzymatic pathways such as the proteasome within motor neurons. The evidence which links an altered autophagy to the onset of motor neuron death proposes that this biochemical pathway might represent a final common mechanism underlying both inherited and sporadic forms of ALS. In light of these findings we also analyze the potential significance of a novel association between ALS, altered autophagy, and mutations of nuclear proteins such as TAR-DNA-Binding Protein 43 and fused in sarcoma/translated in liposarcoma. Such an association appears to be critical since it is now well demonstrated that all sporadic and most familiar forms of ALS are characterized by altered deposition and mislocalization of TAR-DNA-Binding Protein 43. These novel insights into the pathogenesis of ALS may lead to the identification of novel strategies to promote motor neuron survival.
Keywords: Motor neuron, autophagosome, TAR-DNA-binding protein 43, fused in sarcoma/translated in liposarcoma, genetics of amytrophic lateral sclerosis, frontotemporal dementia, ubiquitin proteasome system
CNS & Neurological Disorders - Drug Targets
Title: The Role of Autophagy: What can be Learned from the Genetic Forms of Amyotrophic Lateral Sclerosis
Volume: 9 Issue: 3
Author(s): Livia Pasquali, Riccardo Ruffoli, Federica Fulceri, Sara Pietracupa, Gabriele Siciliano, Antonio Paparelli and Francesco Fornai
Affiliation:
Keywords: Motor neuron, autophagosome, TAR-DNA-binding protein 43, fused in sarcoma/translated in liposarcoma, genetics of amytrophic lateral sclerosis, frontotemporal dementia, ubiquitin proteasome system
Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder caused by loss of motor neurons both in the brain and spinal cord, which dramatically reduces life expectancy. ALS occurs either in familial ALS or, more frequently, in sporadic ALS forms. Several mechanisms have been postulated to underlie motor neuron death. In the present paper, starting from some of the genes related to familial ALS, we overview and discuss their potential role in modifying of the physiological clearance of altered proteins and organelles in motor neurons. Special emphasis is placed on the role of autophagy, which seems to prevail as a protein clearing system over other multienzymatic pathways such as the proteasome within motor neurons. The evidence which links an altered autophagy to the onset of motor neuron death proposes that this biochemical pathway might represent a final common mechanism underlying both inherited and sporadic forms of ALS. In light of these findings we also analyze the potential significance of a novel association between ALS, altered autophagy, and mutations of nuclear proteins such as TAR-DNA-Binding Protein 43 and fused in sarcoma/translated in liposarcoma. Such an association appears to be critical since it is now well demonstrated that all sporadic and most familiar forms of ALS are characterized by altered deposition and mislocalization of TAR-DNA-Binding Protein 43. These novel insights into the pathogenesis of ALS may lead to the identification of novel strategies to promote motor neuron survival.
Export Options
About this article
Cite this article as:
Pasquali Livia, Ruffoli Riccardo, Fulceri Federica, Pietracupa Sara, Siciliano Gabriele, Paparelli Antonio and Fornai Francesco, The Role of Autophagy: What can be Learned from the Genetic Forms of Amyotrophic Lateral Sclerosis, CNS & Neurological Disorders - Drug Targets 2010; 9 (3) . https://dx.doi.org/10.2174/187152710791292594
DOI https://dx.doi.org/10.2174/187152710791292594 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Heart and Brain Axis Targets in CNS Neurological Disorders
Recently there has been a surge of interest in delving deeper into the complex interplay between the heart and brain. This fascination stems from a growing recognition of the profound influence each organ holds over the other, particularly in the realm of central nervous system (CNS) neurological disorders. The purpose ...read more
Lifestyle Interventions to Prevent and Treat Cognitive Impairment and Dementia
More than 55 million people live with dementia worldwide. By 2050, the population affected by dementia will exceed 139 million individuals. Mild cognitive impairment (MCI) is a pre-dementia stage, also known as prodromal dementia, affecting older adults. MCI emerges years before the manifestation of dementia but can be avoidable and ...read more
Pathogenic Proteins in Neurodegenerative Diseases: From Mechanisms to Treatment Modalities
The primary objective of this thematic issue is to elucidate the molecular mechanisms by which pathogenic proteins contribute to neurodegenerative diseases and to highlight current and emerging therapeutic strategies aimed at mitigating their effects. By bringing together cutting-edge research and reviews, this issue aims to: 1.Enhance Understanding: Provide a comprehensive ...read more
Role of glial cells in autism spectrum disorder: Molecular mechanism and therapeutic approaches
Emerging evidence suggests that glial cells may play a pivotal role in neuroanatomical and behavioral changes found in autism spectrum disorder (ASD). Many individuals with ASD experience a neuro-immune system abnormalities throughout life, which implicates a potential role of microglia in the pathogenesis of ASD. Dysfunctional astrocytes and oligodendrocytes were ...read more
![Wayfinder Image](/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
Related Articles
-
Designing Prodrugs Based on Special Residues of Human Serum Albumin
Current Topics in Medicinal Chemistry Stationary Wavelet Transform and AdaBoost with SVM Based Pathological Brain Detection in MRI Scanning
CNS & Neurological Disorders - Drug Targets Radiosensitizing Effect of Electrochemotherapy: A Systematic Review of Protocols and Efficiency
Current Drug Targets Anticancer Natural Coumarins as Lead Compounds for the Discovery of New Drugs
Current Topics in Medicinal Chemistry Medical Treatment of Gastrointestinal Stromal Tumors: State of the Art and Future Perspectives
Reviews on Recent Clinical Trials Non-Viral Nucleic Acid Delivery: Key Challenges and Future Directions
Current Drug Delivery IgG4-Related Disease (IgG4+MOLPS) – Diagnostic Criteria and Diagnostic Problems
Current Immunology Reviews (Discontinued) Recent Patents on Plant-Derived Nanoparticles and their Potential Application Towards Various Cancer Therapeutics
Recent Patents on Anti-Cancer Drug Discovery Nanoemulsions for Skin Targeting: Present Status and Future Prospects
Drug Delivery Letters Molecules of Natural Origin, Semi-synthesis and Synthesis with Anti-Inflammatory and Anticancer Utilities
Current Pharmaceutical Design New Perspectives in Glioblastoma: Nanoparticles-based Approaches
Current Cancer Drug Targets Differentiation-Inducing Therapy for Solid Tumors
Current Pharmaceutical Design Tissue Engineering Techniques in Cardiac Repair and Disease Modelling
Current Pharmaceutical Design Xeno-Cannibalism as an Exacerbation of Self-Cannibalism: A Possible Fruitful Survival Strategy for Cancer Cells
Current Pharmaceutical Design The Mediating Role of miR-451/ETV4/MMP13 Signaling Axis on Epithelialmesenchymal Transition in Promoting Non-small Cell Lung Cancer Progression
Current Molecular Pharmacology Past, Present and Future Strategies of Immunotherapy in Gynecological Malignancies
Current Molecular Medicine Anti-angiogenic Drug Resistance: Roles and Targeting of Non-coding RNAs (microRNAs and long non-coding RNAs)
Current Molecular Pharmacology Radiosynthesis of [18F]-fluorobenzoate-doxorubicin Using Acylation Approach
Current Radiopharmaceuticals Microtubule-targeting Anticancer Agents from Marine Natural Substance
Anti-Cancer Agents in Medicinal Chemistry Molecular Pathology of Sarcomas
Reviews on Recent Clinical Trials