scholarly journals Parkinson’s Disease: Etiology, Neuropathology, and Pathogenesis

2018 ◽  
pp. 3-26 ◽  
Author(s):  
Antonina Kouli ◽  
◽  
Kelli M. Torsney ◽  
Wei-Li Kuan ◽  
◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Etiology

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 Enrichment of risk SNPs in regulatory regions implicate diverse tissues in Parkinson’s disease etiology

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Simon G. Coetzee ◽  
Steven Pierce ◽  
Patrik Brundin ◽  
Lena Brundin ◽  
Dennis J. Hazelett ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Regulatory Regions ◽  
Disease Etiology ◽  
Risk Snps

scholarly journals Genetic Identification of Cell Types Underlying Brain Complex Traits Yields Novel Insights Into the Etiology of Parkinson’s Disease

2019 ◽  
Author(s):  
Julien Bryois ◽  
Nathan G. Skene ◽  
Thomas Folkmann Hansen ◽  
Lisette J.A. Kogelman ◽  
Hunna J. Watson ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Psychiatric Disorders ◽  
Complex Traits ◽  
Cell Types ◽  
Genetic Identification ◽  
Genome Wide Association Studies ◽  
Brain Disorders ◽  
Disease Etiology ◽  
Transcriptomic Data

AbstractGenome-wide association studies (GWAS) have discovered hundreds of loci associated with complex brain disorders, and provide the best current insights into the etiology of these idiopathic traits. However, it remains unclear in which cell types these variants may be active, which is essential for understanding disease etiology and for disease modelling. Here we integrate GWAS results with single-cell transcriptomic data from the entire nervous system to systematically identify cell types underlying psychiatric disorders, neurological conditions, and other brain complex traits. We show that psychiatric disorders are predominantly associated with excitatory neurons from the cortex/hippocampus, medium spiny neurons from the striatum, diverse sets of midbrain neurons, and inhibitory neurons from the cortex/hippocampus. Cognitive traits were generally associated with similar cell types but their associations were driven by different genes. Neurological disorders were associated with different cell types, consistent with other lines of evidence. Notably, we found that Parkinson’s disease is not only genetically associated with dopaminergic neurons but also with serotonergic neurons and cells from the oligodendrocyte lineage. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Altogether, our study provides a solid framework for understanding the cellular basis of complex brain disorders and reveals a new unexpected role of oligodendrocytes in Parkinson’s disease.

scholarly journals Coevolution study of tau and a-synuclein suggests a connection between their normal interaction in neurons and the Parkinson's disease-associated mutation A53T

2021 ◽  
Vol 9 (7) ◽  
Author(s):  
James Gruschus
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Biological Function ◽  
Alpha Synuclein ◽  
Disease Etiology ◽  
Correlated Mutations ◽  
Tubulin Protein ◽  
Synuclein Proteins ◽  
Correlated Mutation

Alpha-synuclein lies at the center of Parkinson’s disease etiology, and polymorphisms in the gene for the microtubule-associated protein tau are risk factors for getting the disease. Tau and a-synuclein interact in vitro, and a-synuclein can also compete with tau binding to microtubules. To test whether these interactions might be part of their natural biological functions, a correlated mutation analysis was performed between tau and a-synuclein, looking for evidence of coevolution. For comparison, analyses were also performed between tau and b- and g-synuclein. In addition, analyses were performed between tau and the synuclein proteins and the neuronal tubulin proteins. Potential correlated mutations were detected between tau and a-synuclein, one involving an a-synuclein residue known to interact with tau in vitro, Asn122, and others involving the Parkinson’s disease-associated mutation A53T. No significant correlated mutations were seen between tau and b- and g-synuclein. Tau showed potential correlated mutations with the neuron-specific bIII-tubulin protein, encoded by the TUBB3 gene. No convincing correlated mutations were seen between the synuclein and tubulin proteins, with the possible exception of b-synuclein with bIVa-tubulin, encoded by the TUBB4A gene. While the correlated mutations between tau and a-synuclein suggest the two proteins have coevolved, additional study will be needed to confirm that their interaction is part of their normal biological function in cells.

Reciprocal Upshot of Nitric Oxide, Endoplasmic Reticulum Stress, and Ubiquitin Proteasome System in Parkinson’s Disease Pathology

2020 ◽  
pp. 107385842094221
Author(s):  
Shubhangini Tiwari ◽  
Sarika Singh
Keyword(s):  
Nitric Oxide ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Neuronal Degeneration ◽  
Early Stage ◽  
Ubiquitin Proteasome System ◽  
Disease Etiology ◽  
Ubiquitin Proteasome

Parkinson’s disease (PD) pathology involves degeneration of nigrostriatal pathway, postulating symptoms associated with age, environment, and genetic anomalies, including nonlinear disease progression. Hallmark characteristics of PD include dopaminergic neuronal degeneration and death, which may also be exhibited by other neurological diseases, making the diagnosis of the disease intricate at early stage. Such obscure diagnosis of the disease, limited symptomatic improvements with available therapeutics, and their inability to modify the disease status instigate us to appraise the past research and formulate the colligating comprehensive insights. This review is accentuating on the role of nitric oxide, endoplasmic reticulum stress, and their association with the ubiquitin proteasome system (UPS) during PD pathology involving focus on ubiquitin ligases due to their regulatory functions. Meticulous understanding of these major disease-related pathological events and their functional alliance may render novel dimensions for better understanding of disease etiology, related mechanisms, as well as direction toward witnessing of new therapeutic targets for the management of Parkinson’s patients.

scholarly journals Systemic deficiency of GM1 ganglioside in Parkinson’s disease tissues and its relation to the disease etiology

2022 ◽  
Author(s):  
Robert Ledeen ◽  
Suman Chowdhury ◽  
Zi-Hua Lu ◽  
Monami Chakraborty ◽  
Gusheng Wu
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Mononuclear Cells ◽  
Occipital Cortex ◽  
Major Type ◽  
Gm1 Ganglioside ◽  
Peripheral Blood Mononuclear ◽  
Disease Etiology ◽  
Blood Mononuclear Cells

AbstractFollowing our initial reports on subnormal levels of GM1 in the substantia nigra and occipital cortex of Parkinson’s disease (PD) patients, we have examined additional tissues from such patients and found these are also deficient in the ganglioside. These include innervated tissues intimately involved in PD pathology such as colon, heart and others, somewhat less intimately involved, such as skin and fibroblasts. Finally, we have analyzed GM1 in peripheral blood mononuclear cells, a type of tissue apparently with no direct innervation, and found those too to be deficient in GM1. Those patients were all afflicted with the sporadic form of PD (sPD), and we therefore conclude that systemic deficiency of GM1 is a characteristic of this major type of PD. Age is one factor in GM1 decline but is not sufficient; additional GM1 suppressive factors are involved in producing sPD. We discuss these and why GM1 replacement offers promise as a disease-altering therapy.

Vulnerability to Parkinson's Disease: Towards an Unifying Theory of Disease Etiology

2011 ◽  
pp. 690-704 ◽  
Author(s):  
B. Marchetti ◽  
F. L'Episcopo ◽  
C. Tirolo ◽  
N. Testa ◽  
S. Caniglia ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Etiology

scholarly journals Natural toxins implicated in the development of Parkinson’s disease

2011 ◽  
Vol 4 (6) ◽  
pp. 361-373 ◽  
Author(s):  
Mohamed Salama ◽  
Oscar Arias-Carrión
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Epidemiological Data ◽  
Experimental Models ◽  
Nocardia Asteroides ◽  
Disease Etiology ◽  
Natural Toxins ◽  
Environmental Component ◽  
Environmental Toxin ◽  
6 Hydroxydopamine

Experimental models of Parkinson’s disease (PD) are of great importance for improving the design of future clinical trials. Various neurotoxic models are available, including 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), paraquat and rotenone. However, no model is considered perfect; each has its own limitations. Based on epidemiological data, a new trend of using environmental toxins in PD modeling seems attractive and has dominated public discussions of the disease etiology. A search for new environmental toxin-based models would improve our knowledge of the pathology of the condition. Here, we discuss some toxins of natural origin (e.g. cycad-derived toxins, epoxomicin, Nocardia asteroides bacteria, Streptomyces venezuelae bacteria, annonacin and DOPAL) that possibly represent a contributory environmental component to PD.

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