Neurocognitive disorders, such as Alzheimer's and Parkinson's, have a wide social impact. These proteinopathies involve misfolded proteins accumulating into neurotoxic aggregates. Mathematical and computational models describing the prion-like dynamics offer an analytical basis to study the diseases' evolution and a computational framework for exploring potential therapies.
View Article and Find Full Text PDFThe Fisher-Kolmogorov equation is a diffusion-reaction PDE that is used to model the accumulation of prionic proteins, which are responsible for many different neurological disorders. Likely, the most important and studied misfolded protein in literature is the Amyloid-$\beta$, responsible for the onset of Alzheimer disease. Starting from medical images we construct a reduced-order model based on a graph brain connectome.
View Article and Find Full Text PDFProc Math Phys Eng Sci
September 2021
The COVID-19 epidemic is the latest in a long list of pandemics that have affected humankind in the last century. In this paper, we propose a novel mathematical epidemiological model named SUIHTER from the names of the seven compartments that it comprises: susceptible uninfected individuals (), undetected (both asymptomatic and symptomatic) infected (), isolated infected (), hospitalized (), threatened (), extinct () and recovered (). A suitable parameter calibration that is based on the combined use of the least-squares method and the Markov chain Monte Carlo method is proposed with the aim of reproducing the past history of the epidemic in Italy, which surfaced in late February and is still ongoing to date, and of validating SUIHTER in terms of its predicting capabilities.
View Article and Find Full Text PDFMaintenance of intracellular proteostasis is essential for neuronal function, and emerging data support the view that disturbed proteostasis plays an important role in brain aging and the pathogenesis of age-related neurodegenerative disorders such as Alzheimer's disease (AD). sAPPalpha (sAPPα), the extracellularly secreted N-terminal alpha secretase cleavage product of the amyloid precursor protein (APP), has an established function in neuroprotection. Recently, we provided evidence that membrane-bound holo-APP functionally cooperates with sAPPα to mediate neuroprotection via activation of the Akt survival signaling pathway and sAPPα directly affects proteostasis.
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