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Numerous degenerative neurological conditions, most notably Parkinson's disease, have been linked to an excessive buildup of alpha synuclein (a-syn) in the brain. Intraneuronal inclusions, often known as Lewy bodies, are neuropathological characteristics seen in Parkinson's disease, Lewy body dementia, and other synucleopathies. The aggregation of a-syn is their main structural component. A-syn accumulation, aggregation, and ensuing Lewy body formation can be attributed to a variety of biological processes. These include genetic changes in parkin, synuclein, or the deubiquitinating enzyme ubiquitin C-terminal hydrolase (UCH-L1), which results in less efficient removal of a-syn via the ubiquitin proteasomal pathway (UPP). Additionally, environmental variables and an age-related decline in antioxidant defense mechanisms that heighten oxidative stress and can have an impact on the formation or clearance of a-syn are intracellular insults.
We focused on changes in the aggregation and clearance of a-syn as impacted by the UPP and the oxidative stress pathways in our dynamic models of a-syn processing in both normal and various disease states. A free radical profile similar to that observed in vivo after exposure to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine is produced during simulation of enhanced oxidative stress (MPTP). To replicate the kinetics of a-syn that correlates to the neuropathology reported for the sporadic and hereditary types of Parkinson's disease, different model parameters of oxidative stress, UPP failure, or both routes are used. With the use of this in silico model, it is possible to evaluate the kinetics of pathway elements and more accurately identify and validate key pharmaceutical targets.
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The mouse and shrew bones were common to all three owls so they were not useful in identifying environments. The gopher bones were unique to the great grey owl of Alaska. Gophers are rodents that are successful in areas with soft soil and lots of grass, so the gopher and this owl would be found in the meadows and evergreen forests of Alaska. The bat was unique to the barking owl of Australia. The bat would be found in woodland habitats where there are many trees the bat can hang from. The gull bones were unique to the short-eared owl of Cuba. Gulls are wetland birds, so the gull and this owl would be found in marshes and coastal areas.
