Commentary - (2024) Volume 7, Issue 3
Received: 01-Jun-2024, Manuscript No. jcnn-24-144497;
Editor assigned: 03-Jun-0024, Pre QC No. P-144497;
Reviewed: 17-Jun-2024, QC No. Q-144497;
Revised: 22-Jun-2024, Manuscript No. R-144497;
Published:
29-Jun-2024
, DOI: 10.37421/2684-6012.2024.7.239
Citation: Chang, Shenglin. “The Impact of Genetic Variants on the Development and Management of Parkinson's disease.” J Clin Neurol Neurosurg 7 (2024): 239.
Copyright: © 2024 Chang S. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Parkinson's Disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms such as tremors, rigidity and bradykinesia, as well as non-motor symptoms including cognitive decline and mood disturbances. The complex etiology of Parkinson's disease has long intrigued researchers, with genetics playing a significant role in both its development and progression. Recent advances in genomics have shed light on how genetic variants influence Parkinson's disease and how this knowledge is shaping the management and treatment of the condition. Genetic variants contribute to Parkinson's disease in several ways, with both rare monogenic and more common polygenic variants implicated. Monogenic Variants are rare, highly penetrant genetic mutations are responsible for Early-Onset Parkinson's Disease (EOPD), which occurs before the age of 50. Mutations in genes such as SNCA, LRRK2, PINK1, PRKN and DJ-1 have been linked to familial forms of Parkinson's disease.
These monogenic forms of Parkinson's disease are relatively rare but provide valuable insights into the disease's pathophysiology. For example, mutations in the SNCA gene, which encodes alpha-synuclein, lead to the accumulation of this protein and the formation of Lewy bodies, a hallmark of Parkinson's disease. The SNCA (Alpha-Synuclein) gene encodes the alpha-synuclein protein, which is a major component of Lewy bodies, the pathological hallmark of Parkinson's disease. Mutations or multiplications of the SNCA gene can lead to the accumulation of alpha-synuclein and its aggregation into toxic forms. This disrupts neuronal function and contributes to the development of Parkinson's disease. The most well-known mutation is the A53T mutation, which has been linked to familial Parkinson's disease [1,2].
Mutations in LRRK2 are one of the most common genetic causes of familial Parkinson's disease and are also associated with sporadic cases. The LRRK2 gene encodes a protein involved in various cellular processes, including vesicle trafficking and cellular signaling. Mutations in this gene, such as G2019S, lead to dysregulation of these processes, contributing to neurodegeneration. Polygenic Risk Factors are unlike monogenic variants, polygenic risk factors involve multiple genes, each contributing a small effect to the overall risk of developing Parkinson's disease. Genome-Wide Association Studies (GWAS) have identified numerous Single Nucleotide Polymorphisms (SNPs) associated with an increased risk of Parkinson's disease. These SNPs are often located in genes involved in cellular processes such as mitochondrial function, immune response and neuronal survival. Examples include variants in the GBA gene, which is involved in lysosomal function and LRRK2, which is implicated in cellular signaling and regulation.
Genetic variants can affect the age at which symptoms first appear. For instance, mutations in PRKN and PINK1 are associated with a younger age of onset, while variations in GBA may lead to a later onset and more severe disease progression. Genetic factors also impact how rapidly the disease progresses. Research indicates that certain genetic variants may be associated with a more aggressive form of Parkinson's disease, characterized by faster motor decline and increased cognitive impairment. Genetic testing can help identify individuals at higher risk for developing Parkinson's disease or those who may have a monogenic form of the disease. This information can be used to tailor preventive strategies and therapeutic interventions. For example, individuals with LRRK2 mutations may benefit from specific treatments targeting the pathways affected by these mutations [3,4].
Identifying genetic variants associated with Parkinson's disease can aid in earlier diagnosis. Early intervention is crucial for managing symptoms and slowing disease progression. Genetic biomarkers may also help in distinguishing Parkinson's disease from other neurodegenerative disorders with similar symptoms. Advances in genomics have paved the way for the development of targeted therapies. For instance, drugs designed to modulate the function of alpha-synuclein, such as antisense oligonucleotides, are being investigated for their potential to treat Parkinson's disease associated with SNCA mutations. Genetic information can enhance the design and efficacy of clinical trials by enabling the selection of participants with specific genetic backgrounds [5]. This approach can improve the likelihood of identifying effective treatments and understanding their impact on different genetic subgroups.
Genetic variants play a critical role in the development and progression of Parkinson's disease. Advances in genetic research are not only enhancing our understanding of the disease but also paving the way for more personalized and effective management strategies. As research continues to evolve, the hope is that these insights will lead to improved outcomes for individuals affected by Parkinson's disease and a better quality of life for patients and their families. The ongoing exploration of the genetic landscape of Parkinson's disease holds promise for further advancements in our understanding and management of the disorder. Large-scale genomic studies and advancements in gene-editing technologies, such as CRISPR/Cas9, may provide new opportunities for targeted therapies and personalized treatment approaches. Additionally, integrating genetic information with other biomarkers and clinical data will be crucial in developing comprehensive management strategies for Parkinson's disease.
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Journal of Clinical Neurology and Neurosurgery received 2 citations as per Google Scholar report
