Abstract
Intensive research over the last 15 years has led to the identification of several autosomal recessive and dominant genes that cause familial Parkinson’s disease (PD). Importantly, the functional characterization of these genes has shed considerable insights into the molecular mechanisms underlying the etiology and pathogenesis of PD. Collectively; these studies implicate aberrant protein and mitochondrial homeostasis as key contributors to the development of PD, with oxidative stress likely acting as an important nexus between the two pathogenic events. Interestingly, recent genome-wide association studies (GWAS) have revealed variations in at least two of the identified familial PD genes (i.e. -synuclein and LRRK2) as significant risk factors for the development of sporadic PD. At the same time, the studies also uncovered variability in novel alleles that is associated with increased risk for the disease. Additionally, in-silico meta-analyses of GWAS data have allowed major steps into the investigation of the roles of gene-gene and gene-environment interactions in sporadic PD. The emergent picture from the progress made thus far is that the etiology of sporadic PD is multi-factorial and presumably involves a complex interplay between a multitude of gene networks and the environment. Nonetheless, the biochemical pathways underlying familial and sporadic forms of PD are likely to be shared.
Keywords: Alpha-synuclein, Parkin, LRRK2, PINK1, DJ-1, GWAS, Protein aggregation, Mitophagy.
Current Genomics
Title:Genetic Insights into Sporadic Parkinson's Disease Pathogenesis
Volume: 14 Issue: 8
Author(s): Chou Chai and Kah-Leong Lim
Affiliation:
Keywords: Alpha-synuclein, Parkin, LRRK2, PINK1, DJ-1, GWAS, Protein aggregation, Mitophagy.
Abstract: Intensive research over the last 15 years has led to the identification of several autosomal recessive and dominant genes that cause familial Parkinson’s disease (PD). Importantly, the functional characterization of these genes has shed considerable insights into the molecular mechanisms underlying the etiology and pathogenesis of PD. Collectively; these studies implicate aberrant protein and mitochondrial homeostasis as key contributors to the development of PD, with oxidative stress likely acting as an important nexus between the two pathogenic events. Interestingly, recent genome-wide association studies (GWAS) have revealed variations in at least two of the identified familial PD genes (i.e. -synuclein and LRRK2) as significant risk factors for the development of sporadic PD. At the same time, the studies also uncovered variability in novel alleles that is associated with increased risk for the disease. Additionally, in-silico meta-analyses of GWAS data have allowed major steps into the investigation of the roles of gene-gene and gene-environment interactions in sporadic PD. The emergent picture from the progress made thus far is that the etiology of sporadic PD is multi-factorial and presumably involves a complex interplay between a multitude of gene networks and the environment. Nonetheless, the biochemical pathways underlying familial and sporadic forms of PD are likely to be shared.
Export Options
About this article
Cite this article as:
Chai Chou and Lim Kah-Leong, Genetic Insights into Sporadic Parkinson's Disease Pathogenesis, Current Genomics 2013; 14 (8) . https://dx.doi.org/10.2174/1389202914666131210195808
DOI https://dx.doi.org/10.2174/1389202914666131210195808 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
Call for Papers in Thematic Issues
Advanced AI Techniques in Big Genomic Data Analysis
The thematic issue on "Advanced AI Techniques in Big Genomic Data Analysis" aims to explore the cutting-edge methodologies and applications of artificial intelligence (AI) in the realm of genomic research, where vast amounts of data pose both challenges and opportunities. This issue will cover a broad spectrum of AI-driven strategies, ...read more
Advanced Computational Algorithms and Artificial Intelligence in Clinical Pharmacogenomics
In the era of personalized medicine, understanding the relationship between genetics and drug response is crucial. This issue delves into innovative methodologies, leveraging deep computational analysis and artificial intelligence, to enhance the field of Clinical Pharmacogenomics. The interdisciplinary approach harnesses the power of advanced high-throughput genotyping technologies, sophisticated computational analysis, ...read more
Applications of Single-cell Sequencing Technology in Reproductive Medicine
Single cell sequencing (SCS) technology utilizes individual cells' genetic material to sequence their genome, transcriptome, and epigenetics at the molecular level. It offers insights into cell heterogeneity and enables the study of limited biological materials. Since its recognition as a valuable technique in 2011, single cell sequencing has yielded numerous ...read more
Current Genomics in Cardiovascular Research
Cardiovascular diseases are the main cause of death in the world, in recent years we have had important advances in the interaction between cardiovascular disease and genomics. In this Research Topic, we intend for researchers to present their results with a focus on basic, translational and clinical investigations associated with ...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
- Announcements
Related Articles
-
Role of Deoxyribonucleoside Kinases and Deoxyribonucleotide Pool Alterations in Nucleoside Reverse Transcriptase Inhibitor Induced Mitochondrial Toxicity
Current Medicinal Chemistry - Anti-Infective Agents Identification of Two Novel Mutations in the <i>ATM</i> Gene from Patients with Ataxia-Telangiectasia by Whole Exome Sequencing
Current Genomics Molecular Diagnostics of Fine Needle Aspiration for the Presurgical Screening of Thyroid Nodules
Current Genomics Smoking and Hypertension: Effects on Clinical, Biochemical and Pathological Variables Due to Isolated or Combined Action on Cardiovascular System
Current Pharmaceutical Design Dietary Antioxidants Significantly Reduced Phorbol Myristate Acetate Induced Oxidative Stress of Peripheral Blood Mononuclear Cells of Patients with Rheumatoid Arthritis
Current Rheumatology Reviews New Avenue of Research: Antiepileptic Drug and Estradiol Neuroprotection in Epilepsy
Recent Patents on CNS Drug Discovery (Discontinued) Non-Analgesic Effects of Opioids: The Interaction of Opioids with Bone and Joints
Current Pharmaceutical Design The Medicinal Chemistry of Genus <i>Aralia</i>
Current Topics in Medicinal Chemistry Epigenetics: New Concepts of Old Phenomena in Vascular Physiology
Current Vascular Pharmacology Omentin: Linking Metabolic Syndrome and Cardiovascular Disease
Current Vascular Pharmacology Staphylococcus aureus: The Toxic Presence of a Pathogen Extraordinaire
Current Medicinal Chemistry Clinical Significance of Thiopurine S-Methyltransferase Gene Polymorphisms
Current Pharmacogenomics Hereditary Rickets. How Genetic Alterations Explain the Biochemical and Clinical Phenotypes
Endocrine, Metabolic & Immune Disorders - Drug Targets Cell-based Treatment of Cerebral Palsy: Still a Long Way Ahead
Current Stem Cell Research & Therapy Membrane Permeable Lipophilic Cations as Mitochondrial Directing Groups
Current Topics in Medicinal Chemistry Aldose Reductase: A Multi-disease Target
Current Enzyme Inhibition ATP Binding Cassette Transporter A1 (ABCA1) Associated Proteins:Potential Drug Targets in the Metabolic Syndrome and Atherosclerotic Disease?
Current Pharmaceutical Biotechnology Drug-Resistance in Central Nervous System Tumors: From the Traditional Cell-Resistance Model to the Genetically Driven Approaches on Therapy
Current Pharmaceutical Biotechnology Allergic Asthma: A Summary from Genetic Basis, Mouse Studies, to Diagnosis and Treatment
Current Pharmaceutical Design Investigating ABCB1-Mediated Drug-Drug Interactions: Considerations for In vitro and In vivo Assay Design
Current Drug Metabolism