AIDD is an integrated tool and a radically new way to discovery new drugs for neurodegenerative diseases (Alzheimer’s, Epilepsy, Ageing, etc.).
Technologies
In this section it is possible to view, also through targeted research, the technologies inserted in the PROMO-TT Database. For further information on the technologies and to contact the CNR Research Teams who developed them, it is necessary to contact the Project Manager (see the references at the bottom of each record card).
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The Biocrystal Facility, a large multidisciplinary laboratory established at the Institute of Molecular Biology and Pathology (IBPM) of CNR, in collaboration with the Biochemistry Department of Sapienza University aims at supporting the italian scientists and the pharmaceutical companies in the research to find new drug and vaccine against the endemic and epidemic diseases through structure-based drug design.
The virtual dynamic docking, carried out in the MOLBD3 lab of the Institute of Biophysics, allows the identification of new drugs through the structural information deriving from the study of target proteins, responsible for some human pathologies. In particular, we screen drugs or small molecules (commercial/own libraries) against known protein sites, surface cavities, surfaces of protein-protein interactions (fixed/rigid hotspots) or structural transition states (dynamic hotspots).
The technology based on cell or tissue cultures is very useful for the production of bioactive compounds. These molecules, depending on the class they belong to, can be used in the food, pharmaceutical and cosmetic industry. In particular, the developed technology is addressed to the optimization of bioactive compounds in plant cell/tissue cultures having the biosynthetic pathway of the compound of interest.
Extracellular vesicles produced by teratocarcinoma cells were isolated and characterized. Functional assays on glioblastoma (GBM) cell cultures showed the inhibitory effect of these vesicles on tumor cell migration, without inducing undesirable effects such as increased cell proliferation or chemotherapy resistance.
We have identified the presence of the poorly characterized precursor proNGF-A in human tissues, deposited its coding nucleotide sequence (GenBank MH358394) and demonstrated its neuroprotective and neurotrophic activity in vitro and in vivo. We inserted mutations into the native molecule, identified through computational analysis, which allow proNGF-A production by eukaryotic expression systems, through a method currently validated on a laboratory scale.
Recently, nanoparticles and nanovesicles have been investigated as potential approaches for the treatment of neurodegenerative diseases. In particular, in the Biotech sector an increasingly deeper penetration of new treatment models and biological drugs based on cellular, subcellular and vesicle therapies is expected. The patent is based on the production of Myelin-based nanoVesicles (MyVes) produced by microfluidics, starting from myelin extracted from brain tissue. These vesicles find two major fields of applications as potential drugs or as supplements/nutraceuticals.
Severe asthma or chronic obstructive pulmonary disease (COPD) are nowadays associated with a poor response to corticosteroids which led to the use of high-dose with consequent improved onset of side effects. The use of nanotechnologies can represent an innovative approach for the effective treatment of both asthma and COPD. The development of new nano-formulations involving the use of nanomaterials and specifically tailored to be inhaled offers numerous advantages over conventional inhaled dosage forms.
We have identified compounds that show a neuroprotective action in vivo, in models of neurodegenerative diseases (e.g. SMA, Parkinson, Alzheimer, Huntington) in the model organism C. elegans. These compounds consist of: mixtures of 22 natural extracts, 15 natural molecules and 11 synthetic molecules.
Combinations of several enzymes in a production chain are preferred to “first generation” enzymatic processes (where the "single reaction - single enzyme" principle was followed), for the synthesis of compounds with high added value starting from simple and cheap substrates. An important requirement for obtaining control in "cascade enzymatic reactions" is the ability to deliver from one biocatalyst to the next one the various intermediates, limiting as much as possible the diffusion of the latter in the solvent.
The environment as well as the food production provide a number of both natural and synthetic compounds whose effects on human being as an organism have not yet been determined nor investigated.
Safe, efficient and specific nano-delivery systems are increasingly needed for precision and regenerative medicine and targeted therapies (e.g. anticancer and antimicrobial therapies), as well as for the cosmetic and nutraceutical sectors’ applications. Despite the appreciable success of synthetic nanovectors, like for example liposomes, their clinical and market application is hampered by some limitations: • large scale production, • low cost production • intrinsic toxicity • limited cellular uptake • limited consumer acceptance.