Parkinson’s disease (PD) is the secondmost prevalent neurodegenerative disorder following Alzheimer’s disease. PD is characterized by debilitating motor symptoms that are primarily caused by cell death of dopaminergic neurons located in the substantia nigra (SN). This degeneration has been heavily linked to the formation of inclusions inside neurons, called Lewy bodies, which contain aggregations of misfolded α-synuclein proteins. The misfolding of α-synuclein is currently postulated to be initiated randomly or by exogenous factors, for instance pesticides or pathogens, entering the intestinal and/or the nasal epithelium, where aggregations form. The aggregations are theorized to progress to the brain from the gut and nose via the vagus nerve and olfacto-ry structures, respectively.
Much research has tried to elucidate the mechanisms behind these hypotheses, but they still remain unclear and will in this investigation be studied in the light of the research question:
To what degree does the evidence support the hypothesis that PD pathology seeds in the gut and/or nose from where it eventually spreads to the SNc? How does this correlate with the current evidence of what causes the aggregationprone misfolding of α-synuclein and the subsequent accumulation of the aggregates, and how these protein aggregates then migrate between neurons?
By collecting a wide variety of data and studies, we have constructed a model of the PD pathology spread; from the proposed initiation in the gut and/or nose to the spreading in the brain. We then critically evaluated the model and concluded that the first event in PD pathology is the misfolding of α-synuclein induced by an exogenous factor, in ENS and neuropod cells, and the olfactory bulb. If clearance mechanisms are impaired, aggregations are then allowed to accumulate into Lewy bodies. Subsequently, α-synuclein aggregations migrate to the brainstem via the vagus nerve or through the olfactory structures, and then lastly to the especially susceptible dopaminergic neurons of the SN, resulting in disease symptoms.
|Uddannelser||Medicinalbiologi, (Bachelor/kandidatuddannelse) Bachelor|
|Udgivelsesdato||16 dec. 2018|
|Vejledere||Nils Ole Dalby|