A5006112900- Alzheimer's disease research and treatments
- Protein Structure and Dynamics
- Ubiquitin and proteasome pathways
- Endoplasmic Reticulum Stress and Disease
- Enzyme Structure and Function
- Prion Diseases and Protein Misfolding
- Trace Elements in Health
- Lipid Membrane Structure and Behavior
- Computational Drug Discovery Methods
- Peptidase Inhibition and Analysis
- Cholinesterase and Neurodegenerative Diseases
- Supramolecular Self-Assembly in Materials
- Spectroscopy and Quantum Chemical Studies
- Glycosylation and Glycoproteins Research
- RNA modifications and cancer
- S100 Proteins and Annexins
- Porphyrin Metabolism and Disorders
- Chemical Synthesis and Analysis
- Drug Transport and Resistance Mechanisms
- Advanced biosensing and bioanalysis techniques
- Neurological diseases and metabolism
- DNA and Nucleic Acid Chemistry
- Genetics and Neurodevelopmental Disorders
- RNA and protein synthesis mechanisms
- Protein Interaction Studies and Fluorescence Analysis
Institute of Crystallography
2019-2024
Consorzio Catania Ricerche
2017-2024
Consorzio Roma Ricerche
2010-2024
National Research Council
2014-2022
Institute of Biostructure and Bioimaging
2011-2020
University of Catania
1999-2019
Istituto Nazionale di Fisica Nucleare, Sezione di Catania
2008-2018
Neami National
2017
National Academies of Sciences, Engineering, and Medicine
2013-2014
Institute for the Dynamics of Environmental Processes
2002
An increasing number of human diseases has been shown to be linked aggregation and amyloid formation by intrinsically disordered proteins (IDPs). Amylin, amyloid-β, α-synuclein are, indeed, involved in type-II diabetes, Alzheimer's, Parkinson's, respectively. Despite the correlation toxicity these at early stages with membrane damage, molecular events underlying process is quite complex understand. In this study, we demonstrate crucial role free lipids lipid–protein complex, which enables an...
The human islet amyloid polypeptide (hIAPP) is the primary component in toxic deposits type-2 diabetes. hIAPP self-assembles to aggregates that permeabilize membranes and constitutes plaques. Uncovering mechanisms of self-assembly key understanding toxicity treatment. Although structurally similar, hIAPP's rat counterpart, (rIAPP), non-toxic. It has been a puzzle why these peptides behave so differently. We combined multiscale modelling theory explain drastically different dynamics rIAPP:...
Abstract Aggregation of the amyloid‐β peptide (Aβ) into fibrillar structures is a hallmark Alzheimer's disease. Thus, preventing self‐assembly Aβ an attractive therapeutic strategy. Here, we used experimental techniques and atomistic simulations to investigate influence carnosine, dipeptide naturally occurring in brain, on aggregation. Scanning force microscopy, circular dichroism thioflavin T fluorescence experiments showed that carnosine does not modify conformational features Aβ42 but...
Alzheimer’s disease is increased in diabetic patients. A defective insulin activity on the brain has been hypothesized to contribute neuronal cell dysregulation leading AD, but mechanism not clear. We analyzed effect of several molecular steps amyloid precursor protein (APP) processing and β-amyloid (Aβ) intracellular accumulation a panel human cells embryonic kidney 293 overexpressing APP-695. The data indicate that insulin, via its own receptor phosphatidylinositol-3-kinase/AKT pathway,...
The self-assembling of the amyloid β (Aβ) peptide into neurotoxic aggregates is considered a central event in pathogenesis Alzheimer's disease (AD). Based on "amyloid hypothesis", many efforts have been devoted to designing molecules able halt progression by inhibiting Aβ self-assembly. Here, we combine biophysical (ThT assays, TEM and AFM imaging), biochemical (WB ESI-MS), computational (all-atom molecular dynamics) techniques investigate capacity four optically pure components natural...
Amyloidogenic proteins are involved in many diseases, including Alzheimer's, Parkinson's, and type II diabetes. These thought to be toxic for cells because of their abnormal interaction with the cell membrane. Simpler model membranes (LUVs) have been used study early steps membrane-protein interactions subsequent evolution. Phospholipid LUVs formed water solution establish a chemical equilibrium between self-assembled small amount phospholipids (CMC). Here, using both experimental molecular...
The aim of this study is to verify if water-soluble porphyrins can be used as proteasome inhibitors. We have found that cationic inhibit peptidase activities much more effectively than the corresponding anionic derivatives. relevance electrostatics in driving porphyin-proteasome interactions has been confirmed by observation inhibitory efficiency macrocycles decreases with number positive substituents. also investigated various metalloporphyrins, which differ due different propension central...
Amylin is a 37-residue peptide hormone produced by the islet β-cells of pancreas and formation amylin aggregates strongly associated with β-cell degeneration in type 2 diabetes, as demonstrated more than 95% patients exhibiting amyloid upon autopsy. It widely recognized that metal ions such copper(II) have been implicated aggregation process amyloidogenic peptides Aβ α-synuclein there evidence self-assembly also largely affected copper(II). For this reason, work, role has investigated...
Appetite for ubiquitin: a gushy travel companion in the intracellular journey of amyloid β peptide.
The largest part of tau secreted from AD nerve terminals and released in cerebral spinal fluid (CSF) is C-terminally truncated, soluble unaggregated supporting potential extracellular role(s) NH
5-Aminomethyl-8-hydroquinoline and its copper(<sc>ii</sc>) complex look very promising in inhibiting cell growth proteasome activity.
Curcumin is recognized for its diverse biological activities, including the ability to induce apoptosis and ferroptosis. Therefore, it represents a promising candidate development of new compounds with neuroprotective anticancer properties. In order synthesize mimics improved pharmacokinetic properties (better solubility stability than curcumin) here, we present design synthesis novel curcumin analogues named Ethylphosphonate-based (EPs), which preserve pharmacophoric features curcumin. New...
Abstract Mitochondrial porin or VDAC (voltage‐dependent anion‐selective channel) is the most abundant protein in mitochondrial outer membrane. The structure of has been predicted to be a transmembrane β‐barrel with an α‐helix at N terminus. It matter debate as whether this putative plays structural role component pore walls function activity. We have synthesised human VDAC1 (HVDAC1) N‐terminal peptide Ac‐AVPPTYADLGKSARDVFTK‐NH 2 ( Prn2 – 20 ) and determined its by CD NMR spectroscopy....
The mechanisms underlying the formation of extracellular amyloid plaques on neuronal membranes, a major hallmark Alzheimer's disease, are subject intense debate. Here we use multiscale simulations and analytical theory to unveil early steps spontaneous self-assembly membrane-embedded α-helical Aβ (1–40) peptides. Based simple model describing electrostatic repulsions among water-exposed charged residues, presence distorted structures called "frustrated helices" is predicted. Large scale (20...
Due to their altered metabolism cancer cells are more sensitive proteasome inhibition or changes of copper levels than normal cells. Thus, the development complexes endowed with features has emerged as a promising anticancer strategy. However, limited information is available about exact mechanism by which inhibits proteasome. Here we show that Cu(II) ions simultaneously inhibit three peptidase activities isolated 20S proteasomes potencies (IC50) in micromolar range. ions, cell-free...