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
Novel Treatments in Subarachnoid Hemorrhage
The current landscape of therapeutic strategies for subarachnoid hemorrhage (SAH), a significant adverse neurological event commonly resulting from the rupture of intracranial aneurysms, is rapidly evolving. Through an in-depth exploration of the natural history of SAH, historical treatment approaches, and emerging management modalities, the present work aims to provide a ...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
![](/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
-
Solenostemma argel: A Rich Source of Very Unusual Pregnane and 14,15- Secopregnane Glycosides with Antiproliferative Activity
Current Organic Chemistry Therapeutic HIV Vaccines
Current Topics in Medicinal Chemistry Recent Advances in Diagnostic and Therapeutic Approaches for Breast Cancer: A Comprehensive Review
Current Pharmaceutical Design Elucidation of Abnormal Extracellular Regulated Kinase (ERK) Signaling and Associations with Syndromic and Non-syndromic Autism
Current Drug Targets Review of Recent Clinical Developments and Patents for the Treatment of Autoimmune and Inflammatory Diseases by Mesenchymal Stromal Cells
Recent Patents on Regenerative Medicine Is HIV Involved in the Pathogenesis of Non-Infectious Pulmonary Complications in Infected Patients?
Current HIV Research Clinical and Translational Research Challenges in Biliary Tract Cancers
Current Medicinal Chemistry Signal Transduction Therapy Targeting Apoptosis Pathways in Cancers
Current Signal Transduction Therapy Thermosensitive Polymeric Hydrogels As Drug Delivery Systems
Current Medicinal Chemistry Calorie Restriction and Dietary Restriction Mimetics: A Strategy for Improving Healthy Aging and Longevity
Current Pharmaceutical Design Reprogramming of Molecular Switching Events in UPR Driven ER Stress: Scope for Development of Anticancer Therapeutics
Current Molecular Medicine Promiscuous Binding Nature of Sh3 Domains to their Target Proteins
Protein & Peptide Letters Modulation of the Type I Interferon Response Defines the Sensitivity of Human Melanoma Cells to Oncolytic Measles Virus
Current Gene Therapy Positron Emission Tomography: Applications In Drug Discovery and Drug Development
Current Topics in Medicinal Chemistry Recent Progress in Phosphoinositide 3-Kinases: Oncogenic Properties and Prognostic and Therapeutic Implications
Current Protein & Peptide Science The Alkylating-HDAC Inhibition Fusion Principle: Taking Chemotherapy to the Next Level with the First in Class Molecule EDO-S101
Anti-Cancer Agents in Medicinal Chemistry Critical Steps in Tissue Processing in Histopathology
Recent Patents on DNA & Gene Sequences SRC: Regulation, Role in Human Carcinogenesis and Pharmacological Inhibitors
Current Pharmaceutical Design The Role of Neuronal Insulin/Insulin-Like Growth Factor-1 Signaling for the Pathogenesis of Alzheimer’s Disease: Possible Therapeutic Implications
CNS & Neurological Disorders - Drug Targets Cell Adhesion Molecules and Cadmium
Current Chemical Biology