Rare coding SNP in DZIP1 gene associated with late-onset sporadic Parkinson's disease

Valente, André; Shin, Joo Heon; Sarkar, Abhijit; Gao, Yuan

doi:10.1038/srep00256

Cited by 10 publications

(7 citation statements)

References 58 publications

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“…The realistic trajectory of NO x reflects a compilation of environmental policies and economic activities 29 . NO x emissions in many industrialized countries are expected to decrease 30 .…”

Section: Discussionmentioning

confidence: 99%

“…NO x emissions in many industrialized countries are expected to decrease 30 . For example, the NO x reductions in Europe in 2010 can be partly attributed to the global economic recession, and partly to the European NO x emission controls 29 . Due to rapid economic development and the coal-dominated energy consumption structure, however, large increases in NO x from China have persisted over the past several decades 31 .…”

Section: Discussionmentioning

confidence: 99%

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Impacts of reactive nitrogen on climate change in China

Shi

Cui

et al. 2015

Sci Rep

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China is mobilizing the largest anthropogenic reactive nitrogen (Nr) in the world due to agricultural, industrial and urban development. However, the climate effects related to Nr in China remain largely unclear. Here we comprehensively estimate that the net climate effects of Nr are −100 ± 414 and 322 ± 163 Tg CO2e on a GTP20 and a GTP100 basis, respectively. Agriculture contributes to warming at 187 ± 108 and 186 ± 56 Tg CO2e on a 20-y and 100-y basis, respectively, dominated by long-lived nitrous oxide (N2O) from fertilized soils. On a 20-y basis, industry contributes to cooling at −287 ± 306 Tg CO2e, largely owing to emissions of nitrogen oxides (NOx) altering tropospheric ozone, methane and aerosol concentrations. However, these effects are short-lived. The effect of industry converts to warming at 136 ± 107 Tg CO2e on a 100-y basis, mainly as a result of the reduced carbon (C) sink from the NOx-induced ozone effect on plant damage. On balance, the warming effects of gaseous Nr are partly offset by the cooling effects of N-induced carbon sequestration in terrestrial ecosystems. The large mitigation potentials through reductions in agricultural N2O and industrial NOx will accompany by a certain mitigation pressure from limited N-induced C sequestration in the future.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Impacts of reactive nitrogen on climate change in China

Shi

Cui

et al. 2015

Sci Rep

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“…Mutations in 13 genes have been associated with these Mendelian inheritable cases of PD, via familial genetic linkage studies. For non-monogenic PD, dozens of single-nucleotide polymorphisms (SNPs) risk factors have been identified based on Genome-Wide Association Studies (GWASs) (2,3,4). Likewise, a number of environmental risk factors (e.g., exposure to metals and pesticides) have been uncovered by epidemiological studies (5).…”

Section: Introductionmentioning

confidence: 99%

“…We have proposed an alternative theory on the origin of sporadic PD, which we term here the Hematopoietic Origin Theory (HOT) (3,16,17). Sporadic PD would be characterized by two phases: an induction phase, followed by a systemic propagation phase.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Methylation Two-Peak Profile Absent in Parkinson’s Disease Patient

Valente

Liao

Rohkin³

et al. 2017

Preprint

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Whole-mitochondrial genome methylation profiles were obtained for mitochondrial DNA (mtDNA) from blood samples of one sporadic Parkinson's Disease (PD) patient and one healthy control donor, via WholeGenome Next-Generation Bisulfite Sequencing. Methylation frequency was determined at 836 CpG sites out of the 1146 CpG sites in mtDNA (73% of the total). The control mtDNA methylation profile exhibited a twopeak frequency distribution, with most CpG sites showing either no methylation, or a methylation above 7%. Instead, the sporadic PD mtDNA methylation profile exhibited a generic bell-shaped frequency distribution. The data is suggestive of the bell-shaped methylation profile arising via a degradation towards randomness of the healthy sample two-peak methylation pattern. Overall, this finding provides a possible explanation for the repeated observation of PD-phenotypic characteristics in cybrid cell lines where solely the mtDNA originates from a PD patient. We discuss the finding in terms of the sporadic PD Hematopoietic Origin Theory (HOT).

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“…A new study by Xiao et al 72 found hematologic abnormalities in alpha-synuclein knock-out mice indicative of a role of alphasynuclein in late-stage hematopoiesis. A genome-wide association study found that a rare nonsynonymous mutation in DZIP1 is a risk factor for PD 73 . DZIP1 is a component of the Hedgehog signaling pathway 74 .…”

Section: A Site Of Origin For the Pd-statementioning

confidence: 99%

The universal non-neuronal nature of Parkinson's disease: A theory

Valente

Adilbayeva

Tokay

et al. 2016

Preprint

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Parkinson's disease (PD) is one of the most common neurodegenerative disorders, yet the etiology of the majority of its cases remains unknown. In this article, relevant published evidence is interpreted and integrated into a comprehensive hypothesis on the nature, origin and intercellular mode of propagation of sporadic PD. We propose to characterize sporadic PD as a pathological deviation in the global gene expression program of a cell: the PD expression-state, or PD-state for short. A universal cell-generic state, the PD-state deviation would be particularly damaging in a neuronal context, ultimately leading to neuron death and the ensuing observed clinical signs. We review why ageing associated accumulated damage caused by oxidative stress in mitochondria could be the trigger for a primordial cell to shift to the PD-state. We propose that hematopoietic cells could be the first to acquire the PD-state, at hematopoiesis, from the disruption in reactive oxygen species (ROS) homeostasis that arises with age in the hematopoietic stem-cell niche. We argue that cellular ageing is nevertheless unlikely to explain the shift to the PD-state of all the subsequently affected cells in a patient, thus indicating the existence of a distinct mechanism of cellular propagation of the PD-state. We highlight recently published findings on the inter-cellular exchange of mitochondrial DNA and the ability of mitochondrial DNA to modulate the cellular global gene expression state and propose this could form the basis for the inter-cellular transmission of the PD-state.

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Rare coding SNP in DZIP1 gene associated with late-onset sporadic Parkinson's disease

Cited by 10 publications

References 58 publications

Impacts of reactive nitrogen on climate change in China

Impacts of reactive nitrogen on climate change in China

Mitochondrial Methylation Two-Peak Profile Absent in Parkinson’s Disease Patient

The universal non-neuronal nature of Parkinson's disease: A theory

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