Introduction
Parkinson’s disease (PD) is a neurodegenerative disease, with prominent motor symptoms (i.e. rigidity, tremors and bradykinesia) [1, 2] and non-motor symptoms [3, 4] (i.e. sleep disorders, constipation, cardiac arrhythmias and cognitive deficits), ultimately leading to death. There are two defining features of PD, degeneration of dopaminergic neurons in the substantia nigra and an abundant amount of -synuclein protein in the brain creating Lewy bodies [5]. When -synuclein misfolds it is insoluble and will aggregate, leading to inclusions within the cell bodies and its intracellular processes [6]. Furthermore, Lewy pathology (LP) can be found in the peripheral nervous system and spinal cord in PD [7]. Alpha-synuclein becomes present …show more content…
A prion is shorthand for a proteinaceous infectious particle with the ability to transform its shape and propagate from cell-to-cell [9]. Similar to prions, infectious -synuclein proteins can turn healthy -synuclein proteins (via a toxic template) into misfolded -synuclein leading to LP. Braak, Del Tredici [10] examined brains of PD as well as asymptomatic individuals’ during intervals post-diagnosis. They believed the olfactory bulb and dorsal motor nucleus of the vagus nerve (DMV) were initially attacked by an infectious agent or environmental pathogen that causes LP, which is then transported throughout the brain retroactively (by neural pathways) [11]. Ultimately, this leads to neuronal death and dysfunction in the brain [12]. Subsequently, four separate case reports [13-16], revealed that implanted dopamine neurons in PD patients showed evidence of LP inclusions 10-22 years post operation. Therefore, -synuclein may be the pathogenic agent spreading PD and it may be mediated in a prion-like manner. These findings initiated the support of PD being a prion-like disorder …show more content…
Despite clinical and experimental evidence supporting the prion-like theory, there are still substantial questions that need to be answered. Critics argue that 1) cultured and animal experiments are not relatable to the human PD, 2) there is not a definite connection between -synuclein, LP and PD symptoms, and 3) -synuclein may not even be the root cause of PD progression. In the first section of this perspective article, in-vitro and in-vivo experiments supporting the prion-like pathology of PD will be discussed. Then, evidence that refute the prion-like pathology of PD will be reviewed. Finally, a conclusion will be made as to whether PD should be classified as a prion-like
Parkinson’s disease (PD) is a neurodegenerative disease, with prominent motor symptoms (i.e. rigidity, tremors and bradykinesia) [1, 2] and non-motor symptoms [3, 4] (i.e. sleep disorders, constipation, cardiac arrhythmias and cognitive deficits), ultimately leading to death. There are two defining features of PD, degeneration of dopaminergic neurons in the substantia nigra and an abundant amount of -synuclein protein in the brain creating Lewy bodies [5]. When -synuclein misfolds it is insoluble and will aggregate, leading to inclusions within the cell bodies and its intracellular processes [6]. Furthermore, Lewy pathology (LP) can be found in the peripheral nervous system and spinal cord in PD [7]. Alpha-synuclein becomes present …show more content…
A prion is shorthand for a proteinaceous infectious particle with the ability to transform its shape and propagate from cell-to-cell [9]. Similar to prions, infectious -synuclein proteins can turn healthy -synuclein proteins (via a toxic template) into misfolded -synuclein leading to LP. Braak, Del Tredici [10] examined brains of PD as well as asymptomatic individuals’ during intervals post-diagnosis. They believed the olfactory bulb and dorsal motor nucleus of the vagus nerve (DMV) were initially attacked by an infectious agent or environmental pathogen that causes LP, which is then transported throughout the brain retroactively (by neural pathways) [11]. Ultimately, this leads to neuronal death and dysfunction in the brain [12]. Subsequently, four separate case reports [13-16], revealed that implanted dopamine neurons in PD patients showed evidence of LP inclusions 10-22 years post operation. Therefore, -synuclein may be the pathogenic agent spreading PD and it may be mediated in a prion-like manner. These findings initiated the support of PD being a prion-like disorder …show more content…
Despite clinical and experimental evidence supporting the prion-like theory, there are still substantial questions that need to be answered. Critics argue that 1) cultured and animal experiments are not relatable to the human PD, 2) there is not a definite connection between -synuclein, LP and PD symptoms, and 3) -synuclein may not even be the root cause of PD progression. In the first section of this perspective article, in-vitro and in-vivo experiments supporting the prion-like pathology of PD will be discussed. Then, evidence that refute the prion-like pathology of PD will be reviewed. Finally, a conclusion will be made as to whether PD should be classified as a prion-like