Signal pathways in aging and neurodegeneration

The current Ph.D. thesis aimed to investigate the signal pathways in aging and neurodegeneration, particularly focusing on the localized and systemic amyloidosis and the corresponding amyloid proteins, thus contributing to novel biomarkers discovery and drug development. Particularly, taking advantage of biochemical and molecular and cellular biology techniques, the current Ph.D. thesis aimed to: 1) investigate misfolded proteins accumulation and inflammatory marker as peripheral prognostic and diagnostic biomarkers for localized amyloidosis, with particular regards to AD and more generally to NDs, establishing their role in reproducing the pathological alterations that occur in the brain also in peripheral tissues, firstly in an animal model of AD and then in NDs patients (i.e. AD and LBDs); 2) explore the influence of ApoE polymorphism on the development of AD-related pathogenic mechanisms, i.e. oxidative stress and misfolded protein accumulation as well as lipid assessment and proteasome activity, also in relation to the lifestyle, in peripheral cells of healthy subject genetically predisposed to develop AD, as putative peripheral prognostic biomarkers; 3) assess the influence of ApoE polymorphism on the cholinergic pathway in a cellular model of AD, i.e. cholinergic-like neurons, evaluating candidate novel central biomarkers and targets for new drug development; 4) compare the stability of TTR fibrils produced by in vitro mechanisms and the ex vivo ones, thus assessing the ability of in vitro models to reproduce the pathology as well as the putative role of kinetic stability of TTR as a biomarker for ATTR and testing TTR-stabilizers as promising drugs.