{"title":"阐明与帕金森病病因的遗传变异相关的生物标志物和分子途径。","authors":"Hai Duc Nguyen","doi":"10.1007/s13760-025-02897-7","DOIUrl":null,"url":null,"abstract":"<p><p>Genetic variants can affect signaling pathways that are important in the pathophysiology of Parkinson's disease (PD). Comprehending their relationship is crucial for the development of diagnostic instruments and preventative drugs for PD. We thoroughly analyzed data from 68 genome-wide association studies to uncover significant genetic variations and clarify the molecular pathways underlying the etiology of Parkinson's disease (PD) resulting from genetic variants. Six common biomarkers linked to PD were found in all 68 investigations: SNCA, TMEM175, BST1, RIT2, LRRK2, and MCCC1. SNCA (↑rs5019538 and ↑rs356182), LRRK2 (↑rs34637584 and ↑rs76904798), and SH3GL2 (↑rs10756907 and ↓rs13294100) were the main biomarkers associated with PD. The clinical traits of PD, such as age at onset, cognitive progression, motor progression, composite progression, tremor dominant, and postural instability gait difficulty, have been found to be underpinned by additional biomarkers, including APOE, NTRK2, SLCO1B3, SLC28A3, AQP10, SNCAIP, ANO2, CADM1, PTPRD, GPR32, GPR321, SQOR, SULT1C2, GABRG2, CYP4Z1, CDH13, and FANCF. Significant evidence was found linking genetic variants linked to an increased risk of PD to reduced dopamine production, receptor recycling, oxidoreductase activity, and increased amyloid-beta accumulation. Considerable evidence links genetic variations with a lower risk of PD due to improved synaptic vesicle signaling, neuron projection development, controlled histone methylation, and excitatory postsynaptic potential. Additionally, we found MYT1L and hsa-miR-20a-5p, which are essential for understanding the genetic variations linked to PD. These findings provide a solid underpinning for future therapeutic approaches aimed at PD, with a focus on the genetic variants and processes connected to the illness.</p>","PeriodicalId":7042,"journal":{"name":"Acta neurologica Belgica","volume":" ","pages":""},"PeriodicalIF":2.1000,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Elucidate biomarkers and the molecular pathways associated with genetic variants that contribute to the etiology of Parkinson's disease.\",\"authors\":\"Hai Duc Nguyen\",\"doi\":\"10.1007/s13760-025-02897-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Genetic variants can affect signaling pathways that are important in the pathophysiology of Parkinson's disease (PD). Comprehending their relationship is crucial for the development of diagnostic instruments and preventative drugs for PD. We thoroughly analyzed data from 68 genome-wide association studies to uncover significant genetic variations and clarify the molecular pathways underlying the etiology of Parkinson's disease (PD) resulting from genetic variants. Six common biomarkers linked to PD were found in all 68 investigations: SNCA, TMEM175, BST1, RIT2, LRRK2, and MCCC1. SNCA (↑rs5019538 and ↑rs356182), LRRK2 (↑rs34637584 and ↑rs76904798), and SH3GL2 (↑rs10756907 and ↓rs13294100) were the main biomarkers associated with PD. The clinical traits of PD, such as age at onset, cognitive progression, motor progression, composite progression, tremor dominant, and postural instability gait difficulty, have been found to be underpinned by additional biomarkers, including APOE, NTRK2, SLCO1B3, SLC28A3, AQP10, SNCAIP, ANO2, CADM1, PTPRD, GPR32, GPR321, SQOR, SULT1C2, GABRG2, CYP4Z1, CDH13, and FANCF. Significant evidence was found linking genetic variants linked to an increased risk of PD to reduced dopamine production, receptor recycling, oxidoreductase activity, and increased amyloid-beta accumulation. Considerable evidence links genetic variations with a lower risk of PD due to improved synaptic vesicle signaling, neuron projection development, controlled histone methylation, and excitatory postsynaptic potential. Additionally, we found MYT1L and hsa-miR-20a-5p, which are essential for understanding the genetic variations linked to PD. These findings provide a solid underpinning for future therapeutic approaches aimed at PD, with a focus on the genetic variants and processes connected to the illness.</p>\",\"PeriodicalId\":7042,\"journal\":{\"name\":\"Acta neurologica Belgica\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2025-09-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta neurologica Belgica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s13760-025-02897-7\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta neurologica Belgica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13760-025-02897-7","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Elucidate biomarkers and the molecular pathways associated with genetic variants that contribute to the etiology of Parkinson's disease.
Genetic variants can affect signaling pathways that are important in the pathophysiology of Parkinson's disease (PD). Comprehending their relationship is crucial for the development of diagnostic instruments and preventative drugs for PD. We thoroughly analyzed data from 68 genome-wide association studies to uncover significant genetic variations and clarify the molecular pathways underlying the etiology of Parkinson's disease (PD) resulting from genetic variants. Six common biomarkers linked to PD were found in all 68 investigations: SNCA, TMEM175, BST1, RIT2, LRRK2, and MCCC1. SNCA (↑rs5019538 and ↑rs356182), LRRK2 (↑rs34637584 and ↑rs76904798), and SH3GL2 (↑rs10756907 and ↓rs13294100) were the main biomarkers associated with PD. The clinical traits of PD, such as age at onset, cognitive progression, motor progression, composite progression, tremor dominant, and postural instability gait difficulty, have been found to be underpinned by additional biomarkers, including APOE, NTRK2, SLCO1B3, SLC28A3, AQP10, SNCAIP, ANO2, CADM1, PTPRD, GPR32, GPR321, SQOR, SULT1C2, GABRG2, CYP4Z1, CDH13, and FANCF. Significant evidence was found linking genetic variants linked to an increased risk of PD to reduced dopamine production, receptor recycling, oxidoreductase activity, and increased amyloid-beta accumulation. Considerable evidence links genetic variations with a lower risk of PD due to improved synaptic vesicle signaling, neuron projection development, controlled histone methylation, and excitatory postsynaptic potential. Additionally, we found MYT1L and hsa-miR-20a-5p, which are essential for understanding the genetic variations linked to PD. These findings provide a solid underpinning for future therapeutic approaches aimed at PD, with a focus on the genetic variants and processes connected to the illness.
期刊介绍:
Peer-reviewed and published quarterly, Acta Neurologica Belgicapresents original articles in the clinical and basic neurosciences, and also reports the proceedings and the abstracts of the scientific meetings of the different partner societies. The contents include commentaries, editorials, review articles, case reports, neuro-images of interest, book reviews and letters to the editor.
Acta Neurologica Belgica is the official journal of the following national societies:
Belgian Neurological Society
Belgian Society for Neuroscience
Belgian Society of Clinical Neurophysiology
Belgian Pediatric Neurology Society
Belgian Study Group of Multiple Sclerosis
Belgian Stroke Council
Belgian Headache Society
Belgian Study Group of Neuropathology