Abstract
Parkinson’s disease (PD) is one of the most common progressive neurodegenerative disorders in modern society. The disease involves many genetic risk factors as well as a sporadic pathogenesis that is age- and environment-dependent. Of particular interest is the formation of intra-neural fibrillar aggregates, namely Lewy bodies (LBs), the histological hallmark of PD, which results from aberrant protein homeostasis or misfolding that results in neurotoxicity. A better understanding of the molecular mechanism and composition of these cellular inclusions will help shed light on the progression of misfolding-associated neurodegenerative disorders. Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is found to co-aggregate with α-synuclein (αS), the major component of LBs. Several familial mutations of UCH-L1, namely p.Ile93Met (p.I93M), p.Glu7Ala (p.E7A), and p.Ser18Tyr (p.S18Y), are associated with PD and other neurodegenerative disorders. Here, we review recent progress and recapitulate the impact of PD-associated mutations of UCH-L1 in the context of their biological functions gleaned from biochemical and biophysical studies. Finally, we summarize the effect of these genetic mutations and post-translational modifications on the association of UCHL1 and PD in terms of loss of cellular functions or gain of cellular toxicity.
Keywords: UCH-L1, α-synuclein, Lewy bodies, Parkinson’s disease, ubiquitin, misfolding.
Current Protein & Peptide Science
Title:Familial Mutations and Post-translational Modifications of UCH-L1 in Parkinson's Disease and Neurodegenerative Disorders
Volume: 18 Issue: 7
Author(s): Yun-Tzai C. Lee and Shang-Te D. Hsu*
Affiliation:
- Institute of Biological Chemistry, Academia Sinica, 128, Section 2, Academia Road, Aipei, 11529,Taiwan,Taiwan
Keywords: UCH-L1, α-synuclein, Lewy bodies, Parkinson’s disease, ubiquitin, misfolding.
Abstract: Parkinson’s disease (PD) is one of the most common progressive neurodegenerative disorders in modern society. The disease involves many genetic risk factors as well as a sporadic pathogenesis that is age- and environment-dependent. Of particular interest is the formation of intra-neural fibrillar aggregates, namely Lewy bodies (LBs), the histological hallmark of PD, which results from aberrant protein homeostasis or misfolding that results in neurotoxicity. A better understanding of the molecular mechanism and composition of these cellular inclusions will help shed light on the progression of misfolding-associated neurodegenerative disorders. Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is found to co-aggregate with α-synuclein (αS), the major component of LBs. Several familial mutations of UCH-L1, namely p.Ile93Met (p.I93M), p.Glu7Ala (p.E7A), and p.Ser18Tyr (p.S18Y), are associated with PD and other neurodegenerative disorders. Here, we review recent progress and recapitulate the impact of PD-associated mutations of UCH-L1 in the context of their biological functions gleaned from biochemical and biophysical studies. Finally, we summarize the effect of these genetic mutations and post-translational modifications on the association of UCHL1 and PD in terms of loss of cellular functions or gain of cellular toxicity.
Export Options
About this article
Cite this article as:
Lee C. Yun-Tzai and Hsu D. Shang-Te*, Familial Mutations and Post-translational Modifications of UCH-L1 in Parkinson's Disease and Neurodegenerative Disorders, Current Protein & Peptide Science 2017; 18 (7) . https://dx.doi.org/10.2174/1389203717666160217143721
DOI https://dx.doi.org/10.2174/1389203717666160217143721 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- 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
-
<i>Withania somnifera</i> in Neurological Disorders: Ethnopharmacological Evidence, Mechanism of Action and its Progress in Delivery Systems
Current Drug Metabolism Neuronal Response of Peroxisomal and Peroxisome-Related Proteins to Chronic and Acute Aβ Injury
Current Alzheimer Research Genistein: A Phytoestrogen with Multifaceted Therapeutic Properties
Mini-Reviews in Medicinal Chemistry Novel Therapeutic Strategies for Dementia
CNS & Neurological Disorders - Drug Targets Commentary (Research Highlights: Wnt-Signalling: A New Direction for Alzheimer Disease?)
CNS & Neurological Disorders - Drug Targets Editorial (Thematic Issue: Current Advances in Biochemistry, Medicinal Chemistry and Drug Development Strategies for Age-Related Neurodegenerative Diseases)
Current Topics in Medicinal Chemistry Growth Hormone/Insulin-Like Growth Factor-I Axis and Insulin in Alzheimers Disease and Its Possible Treatment Usefulness
Central Nervous System Agents in Medicinal Chemistry An Insight into Molecular Mechanisms and Novel Therapeutic Approaches in Epileptogenesis
CNS & Neurological Disorders - Drug Targets Reactive Astrogliosis: Role in Alzheimer's Disease
CNS & Neurological Disorders - Drug Targets Anti-Inflammatory Drugs in Psychiatry
Inflammation & Allergy - Drug Targets (Discontinued) Overview of Proteasome Inhibitor-Based Anti-cancer Therapies: Perspective on Bortezomib and Second Generation Proteasome Inhibitors versus Future Generation Inhibitors of Ubiquitin-Proteasome System
Current Cancer Drug Targets Reorganizing Metals: the Use of Chelating Compounds as Potential Therapies for Metal-Related Neurodegenerative Disease
Current Topics in Medicinal Chemistry Cytosolic Phospholipase A2 Inhibitors as Therapeutic Agents for Neural Cell Injury
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents The Positive Synergism of CPT and MK-801 in Behavioral Tests and in Reduction of Environmental Stress and Redox Signaling Changes in Mice Cerebral Cortex
CNS & Neurological Disorders - Drug Targets IL-17A and Multiple Sclerosis: Signaling Pathways, Producing Cells and Target Cells in the Central Nervous System
Current Drug Targets From Physiome to Pathome: A Systems Biology Model of Major Depressive Disorder and the Psycho-Immune-Neuroendocrine Network
Current Psychiatry Reviews Peptides for Therapy and Diagnosis of Alzheimer's Disease
Current Pharmaceutical Design Stem Cell Therapy: A Promising Approach in Treatment of COVID-19
Current Stem Cell Research & Therapy Evaluation of Current Pharmacological Treatment Options in the Management of Rett Syndrome: From the Present to Future Therapeutic Alternatives.
Current Clinical Pharmacology Lower Frequency of co-Morbid Medical Disorders Related to Poor Impulse Control in Parkinson’s than Alzheimer’s Disease
Current Aging Science