The Universal Non-Neuronal Nature of Parkinson's Disease: A Theory
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...
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doaj-c5ead403535e428c965e459e1c105d3c2020-11-24T22:53:29ZengUniversity Library System, University of PittsburghCentral Asian Journal of Global Health2166-74032016-06-015110.5195/cajgh.2016.231135The Universal Non-Neuronal Nature of Parkinson's Disease: A TheoryAndre X.C.N. Valente0Altynai Adilbayeva1Tursonjan Tokay2Albert Rizvanov3Center for Neuroscience and Cell Biology, University of Coimbra, Cantanhede Biocant - Biotechnology Innovation Center, Cantanhede3Institute of Fundamental Medicine and Biology, Kazan Federal University, KazanNational Laboratory Astana, Nazarbayev University, AstanaInstitute of Fundamental Medicine and Biology, Kazan Federal University, KazanParkinson'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.http://cajgh.pitt.edu/ojs/index.php/cajgh/article/view/231Parkinson's DiseaseNeurodegenerationMitochondria |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andre X.C.N. Valente Altynai Adilbayeva Tursonjan Tokay Albert Rizvanov |
spellingShingle |
Andre X.C.N. Valente Altynai Adilbayeva Tursonjan Tokay Albert Rizvanov The Universal Non-Neuronal Nature of Parkinson's Disease: A Theory Central Asian Journal of Global Health Parkinson's Disease Neurodegeneration Mitochondria |
author_facet |
Andre X.C.N. Valente Altynai Adilbayeva Tursonjan Tokay Albert Rizvanov |
author_sort |
Andre X.C.N. Valente |
title |
The Universal Non-Neuronal Nature of Parkinson's Disease: A Theory |
title_short |
The Universal Non-Neuronal Nature of Parkinson's Disease: A Theory |
title_full |
The Universal Non-Neuronal Nature of Parkinson's Disease: A Theory |
title_fullStr |
The Universal Non-Neuronal Nature of Parkinson's Disease: A Theory |
title_full_unstemmed |
The Universal Non-Neuronal Nature of Parkinson's Disease: A Theory |
title_sort |
universal non-neuronal nature of parkinson's disease: a theory |
publisher |
University Library System, University of Pittsburgh |
series |
Central Asian Journal of Global Health |
issn |
2166-7403 |
publishDate |
2016-06-01 |
description |
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. |
topic |
Parkinson's Disease Neurodegeneration Mitochondria |
url |
http://cajgh.pitt.edu/ojs/index.php/cajgh/article/view/231 |
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