Publications by authors named "Valeria Lanza"

We investigate the therapeutic potential of Aloin A and Aloin B, two natural compounds derived from Aloe vera leaves, focusing on their neuroprotective and anticancer properties. The structural differences between these two epimers suggest that they may exhibit distinct pharmacological properties. Our investigations revealed that both epimers are not stable in aqueous solution and tend to degrade rapidly, with their concentration decreasing by over 50% within approximately 12 h.

View Article and Find Full Text PDF

Lung cancer is the leading cause of death in both men and women, constituting a major public health problem worldwide. Non-small-cell lung cancer accounts for 85%-90% of all lung cancers. We propose a compound that successfully fights tumor growth by targeting the enzyme GARS1.

View Article and Find Full Text PDF

Reactive oxygen species are implicated in several human diseases, including neurodegenerative disorders, cardiovascular dysfunction, inflammation, hereditary diseases, and ageing. Mn-salen complexes are superoxide dismutase (SOD) and catalase (CAT) mimetics, which have shown beneficial effects in various models for oxidative stress. These properties make them well-suited as potential therapeutic agents for oxidative stress diseases.

View Article and Find Full Text PDF

A series of copper(II) complexes with the formula [CuHy()Car%] varying the molecular weight (MW) of Hyaluronic acid (Hy, = 200 or 700 kDa) conjugated with carnosine (Car) present at different loading were synthesized and characterized via different spectroscopic techniques. The metal complexes behaved as Cu, Zn-superoxide dismutase (SOD1) mimics and showed some of the most efficient reaction rate values produced using a synthetic and water-soluble copper(II)-based SOD mimic reported to date. The increase in the percentage of Car moieties parallels the enhancement of the I value determined via the indirect method of Fridovich.

View Article and Find Full Text PDF

Ubiquitin signalling and metal homeostasis play key roles in controlling several physiological cellular activities, including protein trafficking and degradation. While some relationships between these two biochemical pathways have started to surface, our knowledge of their interplay remains limited. Here, we employ a variety of techniques, such as circular dichroism, differential scanning calorimetry, pressure perturbation calorimetry, fluorescence emission, SDS-PAGE, and small-angle X-ray scattering (SAXS) to evaluate the impact of Cu and Zn ions on the structure and stability of K48 linked diubiquitin (K48-Ub), a simple model for polyubiquitin chains.

View Article and Find Full Text PDF

Metal terpyridine complexes have gained substantial interest in many application fields, such as catalysis and supramolecular chemistry. In recent years, the biological activity of terpyridine and its metal complexes has aroused considerable regard. On this basis, we synthesised new terpyridine derivatives of trehalose and glucose to improve the water solubility of terpyridine ligands and target them in cancer cells through glucose transporters.

View Article and Find Full Text PDF

Dipyridamole is currently used as a medication that inhibits blood clot formation and it is also investigated in the context of neurodegenerative and other amyloid related diseases. Here, we propose this molecule as a new diagnostic tool to follow the aggregation properties of three different amyloidogenic proteins tested (insulin, amylin and amyloid β peptide 1-40). Results show that dipyridamole is sensitive to early stage amyloid formation undetected by thioflavin T, giving a different response for the aggregation of the three different proteins.

View Article and Find Full Text PDF

A reduced proteasome activity tiles excessive amyloid growth during the progress of protein conformational diseases (PCDs). Hence, the development of safe and effective proteasome enhancers represents an attractive target for the therapeutic treatment of these chronic disorders. Here we analyze two natural diastereoisomers belonging to the family of flavonolignans, Sil A and Sil B, by evaluating their capacity to increase proteasome activity.

View Article and Find Full Text PDF

Hyaluronic acid (Hy) is a natural linear polymer that is widely distributed in different organisms, especially in the articular cartilage and the synovial fluid. During tissue injury due to oxidative stress, Hy plays an important protective role. All the beneficial properties of Hy make the polymer attractive for many biomedical uses; however, the low stability and short biological half-life limit Hy application.

View Article and Find Full Text PDF

Alzheimer's Diseases (AD) is characterized by the accumulation of amyloid deposits of Aβ peptide in the brain. Besides genetic background, the presence of other diseases and an unhealthy lifestyle are known risk factors for AD development. Albeit accumulating clinical evidence suggests that an impaired lipid metabolism is related to Aβ deposition, mechanistic insights on the link between amyloid fibril formation/clearance and aberrant lipid interactions are still unavailable.

View Article and Find Full Text PDF

Alzheimer's disease (AD) is linked to the abnormal accumulation of amyloid β peptide (Aβ) aggregates in the brain. Silybin B, a natural compound extracted from milk thistle (), has been shown to significantly inhibit Aβ aggregation and to exert neuroprotective properties . However, further explorations of silybin B's clinical potential are currently limited by three main factors: (a) poor solubility, (b) instability in blood serum, and (c) only partial knowledge of silybin's mechanism of action.

View Article and Find Full Text PDF

Copper(II) complexes of the N-terminal peptide fragments of tau protein have been studied by potentiometric and various spectroscopic techniques (UV-vis, CD, ESR and ESI-MS). The octapeptide Tau(9-16) (Ac-EVMEDHAG-NH ) contains the H14 residue of the native protein, while Tau(26-33) (Ac-QGGYTMHQ-NH ) and its mutants Tau(Q26K-Q33K) (Ac-KGGYTMHK-NH ) and Tau(Q26K-Y29A-Q33K) (Ac-KGGATMHK-NH ) include the H32 residue. To compare the binding ability of H14 and H32 in a single molecule the decapeptide Ac-EDHAGTMHQD-NH (Tau(12-16)(30-34)) has also been synthesized and studied.

View Article and Find Full Text PDF

Proteasome malfunction parallels abnormal amyloid accumulation in Alzheimer's Disease (AD). Here we scrutinize a small library of pyrazolones by assaying their ability to enhance proteasome activity and protect neuronal cells from amyloid toxicity. Tube tests evidenced that aminopyrine and nifenazone behave as 20S proteasome activators.

View Article and Find Full Text PDF

Four specifically designed IDE mutants have been used to unveil the molecular basis of peptidase versus E1-like activity of the enzyme. We have found that physiological concentrations of copper(ii) ions inhibit the proteolytic activity of the enzyme towards small and large substrates but have no effect on the E1-like activity of the enzyme.

View Article and Find Full Text PDF

Proliferation and programmed cell death are tightly correlated with the ubiquitin-proteasome system (UPS). Alterations in the UPS may be implicated in pathological conditions such as the proteasome over-activity in cancer cells. Mounting evidence indicates that many types of actively proliferating malignant cells are more sensitive to proteasome inhibition than normal cells, and therefore UPS inhibitors are actively pursued as anticancer agents.

View Article and Find Full Text PDF

The gold(III)-dithiocarbamate complex AuL12 (dibromo [ethyl-N-(dithiocarboxy-kS,kS')-N-methylglycinate] gold(III)), is endowed with promising in vitro/in vivo antitumor activity and toxicological profile. Here, we report our recent strategies to improve its water solubility and stability under physiological conditions along with our efforts for unravelling its tangled mechanism of action. We used three types of α-cyclodextrins (CDs), namely β-CD, Me-β-CD and HP-β-CD to prepare aqueous solutions of AuL12.

View Article and Find Full Text PDF

Background: There is mounting urgency to find new drugs for the treatment of neurodegenerative disorders. A large number of reviews have exhaustively described either the molecular or clinical aspects of neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD). Conversely, reports outlining how known drugs in use for other diseases can also be effective as therapeutic agents in neurodegenerative diseases are less reported.

View Article and Find Full Text PDF

Many biochemical pathways involving nerve growth factor (NGF), a neurotrophin with copper(II) binding abilities, are regulated by the ubiquitin (Ub) proteasome system. However, whether NGF binds Ub and the role played by copper(II) ions in modulating their interactions have not yet been investigated. Herein NMR spectroscopy, circular dichroism, ESI-MS, and titration calorimetry are employed to characterize the interactions of NGF with Ub.

View Article and Find Full Text PDF

Due to their altered metabolism cancer cells are more sensitive to proteasome inhibition or changes of copper levels than normal cells. Thus, the development of copper complexes endowed with proteasome inhibition features has emerged as a promising anticancer strategy. However, limited information is available about the exact mechanism by which copper inhibits proteasome.

View Article and Find Full Text PDF

Transition metal ion complexes of a number of chelators have been widely investigated due to their biological properties. The sugar conjugation of metal complexes has resulted in improved properties of the systems, such as solubility and lectin recognition. In this paper, we report the synthesis, the characterization of new glucose and galactose conjugates of 1,4,8,11-tetraazacyclotetradecane (cyclam) and their Cu(II) complexes.

View Article and Find Full Text PDF

Heptapeptide Semax, encompassing the sequence 4-7 of N-terminal domain of the adrenocorticotropic hormone (ACTH) and a C-terminal Pro-Gly-Pro tripeptide, belongs to a short regulatory peptides family. This compound has been found to affect learning processes and to exert marked neuroprotective activities on cognitive brain functions. Dys-homeostasis of metal ions is involved in several neurodegenerative disorders and growing evidences have showed that brain is a specialized organ able to concentrate metal ions.

View Article and Find Full Text PDF

Many neurodegenerative proteinopathies are characterized by ubiquitin (Ub)-containing intraneuronal inclusion bodies. Recent reports have shown that Ub is able to bind Cu(II) and Zn(II), the dyshomeostasis of which is a hallmark of neurodegeneration. Here we use complementary techniques like potentiometry, circular dichroism-visible, and electron spin resonance to unveil the Ub/metal species that form, at neutral pH, their binding constants and structural features.

View Article and Find Full Text PDF

Carnosine (β-alanyl-L-histidine) is an endogenous dipeptide widely and abundantly distributed in muscle and nervous tissues of several animal species. Many functions have been proposed for this compound, such as antioxidant and metal ion-chelator properties. However, the main limitation on therapeutic use of carnosine on pathologies related to increased oxidative stress and/or metal ion dishomeostasis is associated with the hydrolysis by the specific dipeptidase carnosinase.

View Article and Find Full Text PDF

Mimetics of antioxidant enzymes such as superoxide dismutases (SOD) or catalases are reported as potential new drugs able to reduce oxidative stress damage. In particular, manganese(III) complexes of salen-type ligands have been studied as both SOD and catalase mimetics. In this paper, we report the synthesis of two novel conjugates of salen-type ligands with the beta-cyclodextrin, the 6-deoxy-6-[(S-cysteamidopropyl(1,2-diamino)N,N'-bis(salicylidene))]-beta-cyclodextrin and the 6-deoxy-6-[(S-cysteamidopropyl(1,2-diamino)N,N'-bis(3-methoxysalicylidene))]-beta-cyclodextrin, their spectroscopic characterization, and the synthesis and the characterization of their manganese(III) complexes.

View Article and Find Full Text PDF