Abstract
Gaucher disease is an autosomal recessive lysosomal storage disorder, caused by mutations in the GBA gene. The frequency of Gaucher disease patients and heterozygote carriers that developed Parkinson disease has been found to be above that of the control population. This fact suggests that mutations in the GBA gene can be involved in Parkison’s etiology. Analysis of large cohorts of patients with Parkinson disease has shown that there are significantly more cases bearing GBA mutations than those found among healthy individuals. Functional studies have proven an interaction between α-synuclein and GBA, the levels of which presented an inverse correlation. Mutant GBA proteins cause increases in α-synuclein levels, while an inhibition of GBA by α-synuclein has been also demonstrated. Saposin C, a coactivator of GBA, has been shown to protect GBA from this inhibition. Among the GBA variants associated with Parkinson disease, E326K seems to be one of the most prevalent. Interestingly, it is involved in Gaucher disease only when it forms part of a double-mutant allele, usually with the L444P mutation. Structural analyses have revealed that both residues (E326 and L444) interact with Saposin C and, probably, also with α-synuclein. This could explain the antagonistic role of these two proteins in relation to GBA.
Keywords: Gaucher disease, Parkinson disease, GBA mutations, E326K, L444P, saposin C, α-synuclein.
Current Protein & Peptide Science
Title:Involvement of Gaucher Disease Mutations in Parkinson Disease
Volume: 18 Issue: 7
Author(s): Lluisa Vilageliu and Daniel Grinberg*
Affiliation:
- Departament de Genetica, Facultat de Biología, Universitat de Barcelona, Av. Diagonal 643, E-08028 Barcelona,Spain
Keywords: Gaucher disease, Parkinson disease, GBA mutations, E326K, L444P, saposin C, α-synuclein.
Abstract: Gaucher disease is an autosomal recessive lysosomal storage disorder, caused by mutations in the GBA gene. The frequency of Gaucher disease patients and heterozygote carriers that developed Parkinson disease has been found to be above that of the control population. This fact suggests that mutations in the GBA gene can be involved in Parkison’s etiology. Analysis of large cohorts of patients with Parkinson disease has shown that there are significantly more cases bearing GBA mutations than those found among healthy individuals. Functional studies have proven an interaction between α-synuclein and GBA, the levels of which presented an inverse correlation. Mutant GBA proteins cause increases in α-synuclein levels, while an inhibition of GBA by α-synuclein has been also demonstrated. Saposin C, a coactivator of GBA, has been shown to protect GBA from this inhibition. Among the GBA variants associated with Parkinson disease, E326K seems to be one of the most prevalent. Interestingly, it is involved in Gaucher disease only when it forms part of a double-mutant allele, usually with the L444P mutation. Structural analyses have revealed that both residues (E326 and L444) interact with Saposin C and, probably, also with α-synuclein. This could explain the antagonistic role of these two proteins in relation to GBA.
Export Options
About this article
Cite this article as:
Vilageliu Lluisa and Grinberg Daniel*, Involvement of Gaucher Disease Mutations in Parkinson Disease, Current Protein & Peptide Science 2017; 18 (7) . https://dx.doi.org/10.2174/1389203717666160311115956
DOI https://dx.doi.org/10.2174/1389203717666160311115956 |
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
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...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
-
Potential for Stem Cells Therapy in Alzheimer’s Disease: Do Neurotrophic Factors Play Critical Role?
Current Alzheimer Research Chloride Channels − New Targets for the Prevention of Stroke
Current Vascular Pharmacology Editorial: Impact of Racial Differences on Brain Health among the Oldest Old
Current Alzheimer Research The Role of Uric Acid and Methyl Derivatives in the Prevention of Age-Related Neurodegenerative Disorders
Current Topics in Medicinal Chemistry Intrinsically Disordered Domains, Amyloids and Protein Liquid Phases: Evolving Concepts and Open Questions
Protein & Peptide Letters Cerebral Artery Signal Transduction Mechanisms: Developmental Changes in Dynamics and Ca<sup>2+</sup> Sensitivity
Current Vascular Pharmacology Ginkgolic Acids Confer Potential Anticancer Effects by Targeting Pro- Inflammatory and Oncogenic Signaling Molecules
Current Molecular Pharmacology Sense and Sensibility When Prescribing ‘Off-Label’ to Psychiatric Patients
Current Pharmaceutical Design Management and Treatment of Cardiovascular Diseases in the Elderly
Current Pharmacogenomics and Personalized Medicine Chronic Psychosocial Stress Exacerbates Impairment of Synaptic Plasticity in β-Amyloid Rat Model of Alzheimers Disease: Prevention by Nicotine
Current Alzheimer Research Impact of Cardiovascular Factors on Pulse Wave Velocity and Total Vascular Resistance in Different Age Group Patients with Cardiovascular Disorders
Current Aging Science Humanin: A Possible Linkage Between Alzheimer’s Disease and Type 2 Diabetes
CNS & Neurological Disorders - Drug Targets Amino-Alkyl-Cyclohexanes as a Novel Class of Uncompetitive NMDA Receptor Antagonists
Current Pharmaceutical Design HIV gp120 is an Aberrant Chemoattractant for Blood Resting CD4 T Cells
Current HIV Research Ethnobotanical Treatment Strategies Against Alzheimers Disease
Current Alzheimer Research Omega-3 Polyunsaturated Fatty Acids and Depression: A Review of the Evidence
Current Pharmaceutical Design Neuroprotective Effects of Quercetin: From Chemistry to Medicine
CNS & Neurological Disorders - Drug Targets Aromatase Inhibitors: A New Reality for the Adjuvant Endocrine Treatment of Early-Stage Breast Cancer in Postmenopausal Women
Mini-Reviews in Medicinal Chemistry The Role of Renal Nerve Ablation for the Management of Resistant Hypertension and other Disease Conditions: Benefits and Concerns
Current Vascular Pharmacology Factors of Rapid Cognitive Decline in Late Onset Alzheimer's Disease
Current Aging Science