Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder resulting from degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). PD is characterized by motor dysfunctions as well as gastrointestinal symptoms and mental impairment. The pathological hallmark of PD is an accumulation of misfolded α-synuclein aggregates within the brain. The etiology of PD and related synucleinopathy is poorly understood, but recently, the hypothesis that α-synuclein pathology spreads in a prion-like fashion originating in the gut has gained much scientific attention. A crucial clue was the appearance of constipation before the onset of motor symptoms, gut dysbiosis and synucleinopathy in PD patients. Another line of evidence, demonstrating accumulation of α-synuclein within the peripheral autonomic nervous system (PANS), including the enteric nervous system (ENS), and the dorsal motor nucleus of the vagus (DMV) support the concept that α-synuclein can spread from the ENS to the brain by the vagus nerve. The decreased risk of PD following truncal vagotomy supports this. The convincing evidence of the prion-like behavior of α-synuclein came from postmortem observations that pathological α-synuclein inclusions appeared in healthy grafted neurons. In this review, we summarize the available data from human subjects’ research and animal experiments, which seem to be the most suggestive for explaining the hypotheses.
Highlights
Parkinson’s disease (PD) is a chronic human neurodegenerative disorder, which is characterized by motor dysfunction including tremors, bradykinesia, rigidity and postural instability
Based on the gathered evidence from human and animal research that has been published over the last few decades, it is likely that α-synuclein pathology originating within the gastrointestinal tract spreads via a prion-like mechanism
PD patients are characterized by abnormal gut microbiota composition, impairment of the intestinal barrier and enteric neuro-immune system that lead to enteric inflammation that contributes to neuroinflammation and neurodegeneration in the central nervous system (CNS)
Summary
Parkinson’s disease (PD) is a chronic human neurodegenerative disorder, which is characterized by motor dysfunction including tremors, bradykinesia, rigidity and postural instability. LBs and LNs in the present in olfactory bulb and tract, anterior olfactory nucleus, orbitofrontal cortex, amygdala and hippocampus p-α-syn immunoreactivity in the submucosal neurites synucleinopathy in the olfactory bulb olfactory bulb synucleinopathy density scores correlated significantly with: those in other brain regions (anterior medulla, anterior pons, midbrain, amygdala, gyrus, inferior parietal lobule) mini mental state examinations and UPDRS scale (motor part) score p-α-syn immunoreactivity in the spinal cord and vagus nerve as well as in the submandibular gland, in the submucosa of the lower esophagus, in the stroma of the pancreas, in the submucosa of a primary bronchus, in the submucosa of the larynx, in the adrenal medulla, in the stroma of the parathyroid gland, and in the ovary p-α-syn immunoreactivity in the submucosal neurites and submucosal plexus LP positively correlated with dysarthria and postural instability, constipation severity α-syn mRNA expression in full-thickness sections and intestinal wall layers (submucosa and tunica muscularis) α-syn mRNA expression in myenteric ganglia.
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