scholarly journals Etiology of Parkinson's Disease

2003 ◽  
Vol 30 (S1) ◽  
pp. S10-S18 ◽  
Author(s):  
Zhigao Huang ◽  
Raúl de la Fuente-Fernández ◽  
A. Jon Stoessl
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Environmental Factors ◽  
Neurodegenerative Disorders ◽  
Caffeine Intake ◽  
Genetic Mutations ◽  
Abnormal Protein ◽  
Relative Contribution ◽  
Genetic And Environmental Factors

There is growing recognition that Parkinson's disease (PD) is likely to arise from the combined effects of genetic predisposition as well as largely unidentified environmental factors. The relative contribution of each varies from one individual to another. Even in situations where more than one family member is affected, the predominant influence may be environmental. Although responsible for only a small minority of cases of PD, recently identified genetic mutations have provided tremendous insights into the basis for neurodegeneration and have led to growing recognition of the importance of abnormal protein handling in Parkinson's as well as other neurodegenerative disorders. Abnormal protein handling may increase susceptibility to oxidative stress; conversely, numerous other factors, including oxidative stress and impaired mitochondrial function can lead to impaired protein degradation. A limited number of environmental factors are known to be toxic to the substantia nigra; in contrast, some factors such as caffeine intake and cigarette smoking may protect against the development of PD, although the mechanisms are not established. We review the various genetic and environmental factors thought to be involved in PD, as well as the mechanisms that contribute to selective nigral cell death.

scholarly journals Novel Insights on Genetic and Environmental Factors in Parkinson's Disease from a regional Swedish Case-Control Cohort

2021 ◽  
Author(s):  
Kajsa Brolin ◽  
Sara Bandres Ciga ◽  
Cornelis Blauwendraat ◽  
Hakan Widner ◽  
Per Odin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Environmental Factors ◽  
Environmental Exposures ◽  
Case Control ◽  
Risk Haplotype ◽  
Control Cohort ◽  
Disease Etiology ◽  
Continental Scale ◽  
Genetic And Environmental Factors

BACKGROUND: Risk factors for Parkinson's disease (PD) can be more or less relevant to a population due to population-specific genetic architecture, local lifestyle habits, and environmental exposures. Therefore, it is essential to study PD at a local, regional, and continental scale in order to increase the knowledge on disease etiology. OBJECTIVE: We aimed to investigate the contribution of genetic and environmental factors to PD in a new Swedish case-control cohort. METHODS: PD patients (n=929) and matched population-based controls (n=935) from the southernmost county in Sweden were included in the cohort. Information on environmental exposures was obtained using questionnaires at inclusion. Genetic analyses included a genome-wide association study (GWAS), haplotype assessment, and a risk profile analysis using cumulative genetic risk scores. RESULTS: The cohort is a representative PD case-control cohort (64% men, mean age at diagnosis = 67 years, median Hoehn and Yahr score = 2.0), in which previously reported associations between PD and environmental factors, such as tobacco, could be confirmed. We describe the first GWAS of PD solely composed of PD patients from Sweden, and confirm associations to well-established risk alleles in SNCA. In addition, we identified a potential novel, population-specific PD risk variant in the PLPP4 locus (rs12771445) along with a risk haplotype in the region. CONCLUSIONS: This work provides an in-depth description of a new PD case-control cohort from southern Sweden in which we identified a potential novel PD risk locus, PLPP4. Replication studies are needed to determine whether the PLPP4 locus is associated with PD in Sweden, and on a global scale.

scholarly journals Genetic and Environmental Factors Contributing to Parkinson's Disease: A Case-Control Study in the Cypriot Population

2019 ◽  
Vol 10 ◽  
Author(s):  
Andrea Georgiou ◽  
Christiana A. Demetriou ◽  
Yiolanda P. Christou ◽  
Alexandros Heraclides ◽  
Eleni Leonidou ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Environmental Factors ◽  
Case Control Study ◽  
Case Control ◽  
Genetic And Environmental Factors ◽  
Control Study

scholarly journals Neuroprotective Function of DJ-1 in Parkinson’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Hiroyoshi Ariga ◽  
Kazuko Takahashi-Niki ◽  
Izumi Kato ◽  
Hiroshi Maita ◽  
Takeshi Niki ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Level ◽  
Oxidative Status ◽  
Causative Gene ◽  
Mitochondrial Regulation ◽  
Antioxidative Stress ◽  
Genetic And Environmental Factors ◽  
Neuroprotective Function

Parkinson’s disease (PD) is caused by dopaminergic neuronal death in the substantia nigra, resulting in a reduced level of dopamine in the striatum. Oxidative stress and mitochondrial dysfunction are thought to be major causes of neurodegeneration in PD. Although genetic and environmental factors are thought to affect the onset of PD, precise mechanisms at the molecular level have not been elucidated. TheDJ-1 geneis a causative gene for familial PD (park7) and also an oncogene. DJ-1 has various functions, including transcriptional regulation, antioxidative stress reaction, and chaperone, protease, and mitochondrial regulation, and its activity is regulated by its oxidative status, especially that of cysteine 106 (C106) of DJ-1. Excess oxidation of DJ-1, which renders DJ-1 inactive, has been observed in patients with sporadic PD and Alzheimer’s disease, suggesting that DJ-1 also participates in the onset and pathogenesis of sporadic PD as well as familial PD. DJ-1 is also a stress sensor and its expression is increased upon various stresses, including oxidative stress. In this review, we describe functions of DJ-1 against oxidative stress and possible roles of DJ-1 in the pathogenesis of PD.

scholarly journals The Potential Effects of Oxidative Stress-Related Plasma Abnormal Protein Aggregate Levels on Brain Volume and Its Neuropsychiatric Consequences in Parkinson’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Pei-Chin Chen ◽  
Chiun-Chieh Yu ◽  
Yueh-Sheng Chen ◽  
Cheng-Hsien Lu ◽  
Shan-Ho Chan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Decline ◽  
Brain Volume ◽  
Mediation Model ◽  
Protein Aggregate ◽  
Abnormal Protein ◽  
Regional Brain ◽  
Regional Brain Volume

Background. Oxidative stress has been implicated in the pathogenesis of many diseases, including Parkinson’s disease. Large protein aggregates may be produced after the breakdown of the proteostasis network due to overt oxidative stress. Meanwhile, brain volume loss and neuropsychiatric deficits are common comorbidities in Parkinson’s disease patients. In this study, we applied a mediation model to determine the potential influences of oxidative stress-related plasma abnormal protein aggregate levels on brain volume and neuropsychiatric consequences in Parkinson’s disease. Method. 31 patients with PD and 24 healthy controls participated in this study. The PD patients were further grouped according to the presentation of cognitive decline or not. All participants received complete examinations to determine plasma abnormal protein aggregates levels, brain volume, and neuropsychiatric performance. The results were collected and analyzed in a single-level three-variable mediation model. Results. Patients with PD cognitive decline exhibited higher plasma NfL levels, decreased regional brain volume, and poor neuropsychiatric subtest results compared with PD patients with normal cognition, with several correlations among these clinical presentations. The mediation model showed that the superior temporal gyrus completely mediated the effects of elevated plasma NfL levels due to the poor psychiatric performance of picture completion and digit span. Conclusion. This study provides insight into the effects of oxidative stress-related plasma abnormal protein aggregate levels on regional brain volume and neuropsychiatric consequences in Parkinson’s disease patients.

scholarly journals Curcumin Effectively Rescued Parkinson’s Disease-Like Phenotypes in a Novel Drosophila melanogaster Model with dUCH Knockdown

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Thi Thanh Nguyen ◽  
My Dung Vuu ◽  
Man Anh Huynh ◽  
Masamitsu Yamaguchi ◽  
Linh Thuoc Tran ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Genetic Factors ◽  
Neurodegenerative Disorder ◽  
Appropriate Therapy ◽  
Genetic And Environmental Factors ◽  
The Relationship ◽  
Common Neurodegenerative Disorder

The relationship between oxidative stress and neurodegenerative diseases has been extensively examined, and antioxidants are considered to be a promising approach for decelerating disease progression. Parkinson’s disease (PD) is a common neurodegenerative disorder and affects 1% of the population over 60 years of age. A complex combination of genetic and environmental factors contributes to the pathogenesis of PD. However, since the onset mechanisms of PD have not yet been elucidated in detail, difficulties are associated with developing effective treatments. Curcumin has been reported to have neuroprotective properties in PD models induced by neurotoxins or genetic factors such as α-synuclein, PINK1, DJ-1, and LRRK2. In the present study, we investigated the effects of curcumin in a novel Drosophila model of PD with knockdown of dUCH, a homolog of human UCH-L1. We found that dopaminergic neuron-specific knockdown of dUCH caused impaired movement and the loss of dopaminergic neurons. Furthermore, the knockdown of dUCH induced oxidative stress while curcumin decreased the ROS level induced by this knockdown. In addition, dUCH knockdown flies treated with curcumin had improved locomotive abilities and less severe neurodegeneration. Taken together, with studies on other PD models, these results strongly suggest that treatments with curcumin are an appropriate therapy for PD related to oxidative stress.

scholarly journals In Vitro Assessment of the Neuroprotective and Antioxidant Properties of New Benzimidazole Derivatives as Potential Drug Candidates for the Treatment of Parkinson’s Disease

Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 54
Author(s):  
Anastassova ◽  
Argirova ◽  
Yancheva ◽  
Aluani ◽  
Tzankova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorders ◽  
Antioxidant Properties ◽  
Benzimidazole Derivatives ◽  
Potential Drug ◽  
Drug Candidates ◽  
In Vitro Assessment

Oxidative stress is related to the pathogenesis of many neurodegenerative disorders, including [...]

scholarly journals Insights on Genetic and Environmental Factors in Parkinson’s Disease from a Regional Swedish Case-Control Cohort

2021 ◽  
pp. 1-20
Author(s):  
Kajsa Brolin ◽  
Sara Bandres-Ciga ◽  
Cornelis Blauwendraat ◽  
Håkan Widner ◽  
Per Odin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Environmental Factors ◽  
Genetic Risk ◽  
Environmental Exposures ◽  
Case Control ◽  
Control Cohort ◽  
Genome Wide ◽  
Genetic And Environmental Factors

Background: Risk factors for Parkinson’s disease (PD) can be more or less relevant to a population due to population-specific genetic architecture, local lifestyle habits, and environmental exposures. Therefore, it is essential to study PD at a local, regional, and continental scale in order to increase the knowledge on disease etiology. Objective: We aimed to investigate the contribution of genetic and environmental factors to PD in a new Swedish case-control cohort. Methods: PD patients (n = 929) and matched population-based controls (n = 935) from the southernmost county in Sweden were included in the cohort. Information on environmental exposures was obtained using questionnaires at inclusion. Genetic analyses included a genome-wide association study (GWAS), haplotype assessment, and a risk profile analysis using cumulative genetic risk scores. Results: The cohort is a representative PD case-control cohort (64%men, mean age at diagnosis = 67 years, median Hoehn and Yahr score 2.0), in which previously reported associations between PD and environmental factors, such as tobacco, could be confirmed. We describe the first GWAS of PD solely composed of PD patients from Sweden, and confirm associations to well-established risk alleles in SNCA. In addition, we nominate an unconfirmed and potentially population-specific genome-wide significant association in the PLPP4 locus (rs12771445). Conclusion: This work provides an in-depth description of a new PD case-control cohort from southern Sweden, giving insights into environmental and genetic risk factors of PD in the Swedish population.

Sign in / Sign up

Export Citation Format

Share Document