Effect of zonisamide co-administration with levodopa on global gene expression in the striata of rats with Parkinson’s disease

2012 ◽  
Vol 428 (3) ◽  
pp. 401-404 ◽  
Author(s):  
Yuto Ueda ◽  
Shoko Tokashiki ◽  
Ai Kanemaru ◽  
Toshio Kojima
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Global Gene Expression

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

2015 ◽  
Author(s):  
André Valente ◽  
Altynay Adilbayeva ◽  
Tursonjan Tokay ◽  
Albert Rizvanov
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dna ◽  
Late Onset ◽  
Clinical Signs ◽  
Global Gene Expression ◽  
Neuron Death ◽  
Hematopoietic Stem ◽  
Hematopoietic Stem Cell Niche

Various recent developments of relevance to Parkinson's disease (PD) are discussed and integrated into a comprehensive hypothesis on the nature, origin and inter-cellular mode of propagation of late-onset sporadic PD. We propose to define sporadic PD as a characteristic pathological deviation in the global gene expression program of a cell: the PD expression-state, or PD-state for short. Although 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 age accumulated damage caused by oxidative stress in mitochondria could be the trigger for a primordial cell to shift to the PD-state. We put forward 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 why, nonetheless, such a process is 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 propagation of the PD-state. We highlight recent findings on the intercellular 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 intercellular propagation of the PD-state.

scholarly journals C. elegans genetic background modifies the core transcriptional response in an α-synuclein model of Parkinson’s disease

2018 ◽  
Author(s):  
Yiru A. Wang ◽  
Basten L. Snoek ◽  
Mark G. Sterken ◽  
Joost A.G. Riksen ◽  
Jana J. Stastna ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Background ◽  
Expression Patterns ◽  
Transcriptional Response ◽  
Global Gene Expression ◽  
C Elegans ◽  
The Core ◽  
Repair Mechanisms

AbstractAccumulation of protein aggregates is a major cause of Parkinson’s disease (PD), a progressive neurodegenerative condition that is one of the most common causes of dementia. Transgenic Caenorhabditis elegans worms expressing the human synaptic protein α-synuclein show inclusions of aggregated protein and replicate the defining pathological hallmarks of PD. It is however not known how PD progression and pathology differs among individual genetic backgrounds. Here, we compared gene expression patterns, and investigated the phenotypic consequences of transgenic α-synuclein expression in five different C. elegans genetic backgrounds. Transcriptome analysis indicates that the effects of -synuclein expression on pathways associated with nutrient storage, lipid transportation and ion exchange depend on the genetic background. The gene expression changes we observe suggest that a range of phenotypes will be affected by α-synuclein expression. We experimentally confirm this, showing that the transgenic lines generally show delayed development, reduced lifespan, and an increased rate of matricidal hatching. These phenotypic effects coincide with the core changes in gene expression, linking developmental arrest, mobility, metabolic and cellular repair mechanisms to α-synuclein expression. Together, our results show both genotype-specific effects and core alterations in global gene expression and in phenotype in response to -synuclein. We conclude that the PD effects are substantially modified by the genetic background, illustrating that genetic background mechanisms should be elucidated to understand individual variation in PD.

scholarly journals The Universal Non-Neuronal Nature of Parkinson's Disease: A Theory

2016 ◽  
Vol 5 (1) ◽  
Author(s):  
Andre X.C.N. Valente ◽  
Altynai Adilbayeva ◽  
Tursonjan Tokay ◽  
Albert Rizvanov
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dna ◽  
Clinical Signs ◽  
Global Gene Expression ◽  
Neuron Death ◽  
Hematopoietic Stem ◽  
Hematopoietic Stem Cell Niche ◽  
Published Evidence

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 manuscript, relevant published evidence is interpreted and integrated into a comprehensive hypothesis on the nature, origin, and inter-cellular 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 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.

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

2016 ◽  
Author(s):  
André Valente ◽  
Altynay Adilbayeva ◽  
Tursonjan Tokay ◽  
Albert Rizvanov
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dna ◽  
Clinical Signs ◽  
Global Gene Expression ◽  
Neuron Death ◽  
Hematopoietic Stem ◽  
Published Evidence ◽  
A Cell

Parkinson's disease (PD) is one of the most common neurodegenerative disorders, yet the etiology of themajority of its cases remains unknown. In here, relevant published evidence is interpreted and integrated into a comprehensive hypothesis on the nature, origin and inter-cellular 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 age accumulated damage caused by oxidative stress in mitochondria could be the trigger for a primordial cell to shift to the PD-state. We put forward 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 why, nonetheless, a cell ageing process is 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 recent findings on the intercellular 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 intercellular propagation of the PD-state.

The Effect of Dopamine on Gene Expression of Alpha-synuclein and Transcription Factors GATA-1, GATA-2, and ZSCAN21 in Parkinson’s Disease

2018 ◽  
Vol 12 (5) ◽  
pp. 410-418
Author(s):  
A. K. Emelyanov ◽  
A. O. Lavrinova ◽  
E. M. Litusova ◽  
N. A. Knyazev ◽  
D. G. Kulabukhova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factors ◽  
Alpha Synuclein

Gene expression of the nicotinic acetylcholine receptor α4 subunit in the frontal cortex in Parkinson's disease patients

1995 ◽  
Vol 187 (3) ◽  
pp. 173-176 ◽  
Author(s):  
Hannsjörg Schröder ◽  
Robert A.I. de Vos ◽  
Ernst N.H. Jansen ◽  
Christina Birtsch ◽  
Andrea Wevers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Frontal Cortex ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine

scholarly journals Molecular and functional variation in iPSC-derived sensory neurons

2017 ◽  
Author(s):  
Jeremy Schwartzentruber ◽  
Stefanie Foskolou ◽  
Helena Kilpinen ◽  
Julia Rodrigues ◽  
Kaur Alasoo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Chromatin Accessibility ◽  
Nervous System Development ◽  
Sensory Function ◽  
Neuronal Cultures ◽  
Common Disease ◽  
Specific Method ◽  
Causal Variants

AbstractInduced pluripotent stem cells (iPSCs), and cells derived from them, have become key tools to model biological processes and disease mechanisms, particularly in cell types such as neurons that are difficult to access from living donors. Here, we present the first map of regulatory variants in an iPSC-derived cell type. To investigate genetic contributions to human sensory function, we performed 123 differentiations of iPSCs from 103 unique donors to a sensory neuronal fate, and measured gene expression, chromatin accessibility, and neuronal excitability. Compared with primary dorsal root ganglion, where sensory nerves collect near the spinal cord, gene expression was more variable across iPSC-derived neuronal cultures, particularly in genes related to differentiation and nervous system development. Single cell RNA-sequencing revealed that although the majority of cells are neuronal and express the expected marker genes, a substantial fraction have a fibroblast-like expression profile. By applying an allele-specific method we identify 3,778 quantitative trait loci influencing gene expression, 6,318 for chromatin accessibility, and 2,097 for RNA splicing at FDR 10%. A number of these overlap with common disease associations, and suggest candidate causal variants and target genes. These include known causal variants at SNCA for Parkinson’s disease and TNFRSF1A for multiple sclerosis, as well as new candidates for migraine, Parkinson’s disease, and schizophrenia.

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