Danilo Milardi

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The theoretical analysis of the protein denaturation model which includes an irreversible, exothermic and rate-limited step has been improved and applied to the DSC profile of Azurin. The two-step nature of the irreversible denaturation of globular proteins is usually depicted in the following simplified scheme: N <--> U <--> F, which is known as the Lumry(More)
Interest in the 37-residue human islet amyloid polypeptide (hIAPP) is related to its ability to form amyloid deposits in patients affected by type II diabetes. Attempts to unravel the molecular features of this disease have indicated several regions of this polypeptide to be responsible for either the ability to form insoluble fibrils or the abnormal(More)
Alzheimer's disease is increased in diabetic patients. A defective insulin activity on the brain has been hypothesized to contribute to the neuronal cell dysregulation leading to AD, but the mechanism is not clear. We analyzed the effect of insulin on several molecular steps of amyloid precursor protein (APP) processing and β-amyloid (Aβ) intracellular(More)
Although the molecular determinants of Familial Amyotrophic Lateral Sclerosis (FALS) are still largely unknown, previous studies have demonstrated that aggregation of Cu, Zn superoxide dismutase (SOD1) mutants may play a causative role in FALS. It has been proposed that this pathogenic process occurs via a multi-step pathway involving metal loss, dimer(More)
Disruption of the integrity of the plasma membrane by amyloidogenic proteins is linked to the pathogenesis of a number of common age-related diseases. Although accumulating evidence suggests that adverse environmental stressors such as unbalanced levels of metal ions may trigger amyloid-mediated membrane damage, many features of the molecular mechanisms(More)
The mechanisms underlying the formation of extracellular amyloid plaques on neuronal membranes, a major hallmark of Alzheimer's disease, are the subject of intense debate. Here we use multiscale simulations and analytical theory to unveil the early steps of the spontaneous self-assembly of membrane-embedded α-helical Aβ (1-40) peptides. Based on a simple(More)
The thermal denaturation of plastocyanin in aqueous solution was investigated by means of DSC, ESR and absorbance techniques, with the aim of determining the thermodynamic stability of the protein and of characterizing the thermally induced conformational changes of its active site. The DSC and absorbance experiments indicated an irreversible and(More)
An abnormal interaction between copper and the prion protein is believed to play a pivotal role in the pathogenesis of prion diseases. Copper binding has been mainly attributed to the N-terminal domain of the prion protein, but this hypothesis has recently been challenged in some papers which suggest that the C-terminal domain might also compete for metal(More)
Aggregation of the amyloid-β peptide (Aβ) into fibrillar structures is a hallmark of Alzheimer's disease. Thus, preventing self-assembly of the Aβ peptide is an attractive therapeutic strategy. Here, we used experimental techniques and atomistic simulations to investigate the influence of carnosine, a dipeptide naturally occurring in the brain, on Aβ(More)
The human islet amyloid polypeptide (hIAPP) is the primary component in the toxic islet amyloid deposits in type-2 diabetes. hIAPP self-assembles to aggregates that permeabilize membranes and constitutes amyloid plaques. Uncovering the mechanisms of amyloid self-assembly is the key to understanding amyloid toxicity and treatment. Although structurally(More)