Genetic Risk Profiling in Parkinson’s Disease and Utilizing Genetics to Gain Insight into Disease-Related Biological Pathways

Hall, Ashley; Bandrés‐Ciga, Sara; Díez-Fairén, Mónica; Quinn, John P.; Billingsley, Kimberley

doi:10.3390/ijms21197332

Cited by 22 publications

(20 citation statements)

References 110 publications

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“…Furthermore, substantial cumulative risk was reported by risk profile analysis [51]. GSA generated polygenic risk scores (PRS) for prediction of risk and progression of Parkinson's disease (PD), to search PD-related biological pathways from large-scale pathway specific-genetic risk profiling, and to identify causal PD genes and potential therapeutic targets [52]. Furthermore, increasing evidence suggests that epigenetic mechanisms play a role in regulation of PD-associated genes, including DNA methylation, histone modifications, and microRNAs (miRNSs) [53].…”

Section: Discussionmentioning

confidence: 99%

Single Nucleotide Polymorphisms of Indoleamine 2,3-Dioxygenase Influenced the Age Onset of Parkinson’s Disease

Török¹,

Maszlag-Török²,

Molnár³

et al. 2021

Preprint

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Aims Earlier studies reported alterations of the kynurenine (KYN) pathway of tryptophan (TRP) metabolism in Parkinson’s disease (PD). The first rate-limiting enzymes indoleamine 2,3- dioxygenase (IDO) and tryptophan dioxygenase were observed upregulated, resulting elevated KYN/TRP ratios in the serum and cerebrospinal fluid samples of patients with PD. An increasing number of single nucleotide polymorphisms (SNPs) has been identified in a population of PD. However, little is known if genetic variations of the IDO contribute to disturbance of the KYN metabolism in and the pathogenesis of PD. Main methods SNP analysis of IDO1 was performed by allelic discrimination assay with fluorescently labelled TaqMan probes and a subgroup analysis was conducted according to the age of PD onset. The frame shifts variant rs34155785, intronic variant rs7820268, and promotor region variant rs9657182 SNPs of 105 PD patients without comorbidity were analyzed and compared to 129 healthy controls. Key findings No significant correlation was found in three SNPs between PD patients and healthy controls. However, the subgroup analysis revealed that A alleles of rs7820268 SNP or rs9657182 SNP carriers contribute to later onset of PD than non-carriers. Significance The study suggested that SNPs of IDO1 influenced the age onset of PD and genotyping of SNPs in certain alleles potentially serves as a risk biomarker of PD.

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Section: Discussionmentioning

confidence: 99%

Single Nucleotide Polymorphisms of Indoleamine 2,3-Dioxygenase Influenced the Age Onset of Parkinson’s Disease

Török¹,

Maszlag-Török²,

Molnár³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Genetics can be used in multiple ways to identify potential genes, proteins, pathways, and networks that may be involved in the pathogenesis of PD and could potentially be therapeutically targeted [ 50 ]. The simplest way of identifying targets using genetics is by examining genes known to cause disease or increase risk, like LRRK2 and GBA , using linkage and sequencing studies in families and sporadic cases.…”

Section: Genetics As a Tool To Nominate Network To Be Targeted Inmentioning

confidence: 99%

Advancing Personalized Medicine in Common Forms of Parkinson’s Disease through Genetics: Current Therapeutics and the Future of Individualized Management

Reed

Schumacher-Schuh

et al. 2021

JPM

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Parkinson’s disease (PD) is a condition with heterogeneous clinical manifestations that vary in age at onset, rate of progression, disease course, severity, motor and non-motor symptoms, and a variable response to antiparkinsonian drugs. It is considered that there are multiple PD etiological subtypes, some of which could be predicted by genetics. The characterization and prediction of these distinct molecular entities provides a growing opportunity to use individualized management and personalized therapies. Dissecting the genetic architecture of PD is a critical step in identifying therapeutic targets, and genetics represents a step forward to sub-categorize and predict PD risk and progression. A better understanding and separation of genetic subtypes has immediate implications in clinical trial design by unraveling the different flavors of clinical presentation and development. Personalized medicine is a nascent area of research and represents a paramount challenge in the treatment and cure of PD. This manuscript summarizes the current state of precision medicine in the PD field and discusses how genetics has become the engine to gain insights into disease during our constant effort to develop potential etiological based interventions.

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“…Genetic factors that cause or increase risk of developing PD include mutations in SNCA (encoding α-synuclein), PRKN , and DJ-1 , among others ( Hall et al, 2020 ). Interestingly, several of these genetic factors have been shown to contribute to immune defense against infectious agents.…”

Section: Introductionmentioning

confidence: 99%

“…Authors showed this to be due to enhanced phagocytosis and bactericidal activity in DJ-1 -deficient macrophages, adoptive transfer of which could rescue septic wildtype mice ( Amatullah et al, 2016 ). Although genetic mutations account for only 5–15% of all PD cases ( Hall et al, 2020 ), better understanding these genetic causes of disease have informed the pathophysiology of the more common sporadic disease cases.…”

Section: Introductionmentioning

confidence: 99%

Microbial Infections Are a Risk Factor for Neurodegenerative Diseases

Lotz

Blackhurst

Reagin

et al. 2021

Front. Cell. Neurosci.

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Neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, comprise a family of disorders characterized by progressive loss of nervous system function. Neuroinflammation is increasingly recognized to be associated with many neurodegenerative diseases but whether it is a cause or consequence of the disease process is unclear. Of growing interest is the role of microbial infections in inciting degenerative neuroinflammatory responses and genetic factors that may regulate those responses. Microbial infections cause inflammation within the central nervous system through activation of brain-resident immune cells and infiltration of peripheral immune cells. These responses are necessary to protect the brain from lethal infections but may also induce neuropathological changes that lead to neurodegeneration. This review discusses the molecular and cellular mechanisms through which microbial infections may increase susceptibility to neurodegenerative diseases. Elucidating these mechanisms is critical for developing targeted therapeutic approaches that prevent the onset and slow the progression of neurodegenerative diseases.

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Genetic Risk Profiling in Parkinson’s Disease and Utilizing Genetics to Gain Insight into Disease-Related Biological Pathways

Cited by 22 publications

References 110 publications

Single Nucleotide Polymorphisms of Indoleamine 2,3-Dioxygenase Influenced the Age Onset of Parkinson’s Disease

Single Nucleotide Polymorphisms of Indoleamine 2,3-Dioxygenase Influenced the Age Onset of Parkinson’s Disease

Advancing Personalized Medicine in Common Forms of Parkinson’s Disease through Genetics: Current Therapeutics and the Future of Individualized Management

Microbial Infections Are a Risk Factor for Neurodegenerative Diseases

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