The universal non-neuronal nature of Parkinson's disease: A theory
- Published
- Accepted
- Subject Areas
- Cell Biology, Neurology
- Keywords
- Parkinsons disease, Neurodegenerative diseases, Mitochondria, Parkinson's disease, Neurodegeneration
- Copyright
- © 2016 Valente et al.
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Preprints) and either DOI or URL of the article must be cited.
- Cite this article
- 2016. The universal non-neuronal nature of Parkinson's disease: A theory. PeerJ Preprints 4:e1314v4 https://doi.org/10.7287/peerj.preprints.1314v4
Abstract
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 observerd clinical signs. We review why ageing 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 expression gene state and propose this could form the basis for the inter-cellular transmission of the PD-state.
Author Comment
This is the final version to appear in Central Asian Journal of Global Health (2016).