Peptides as modulators of α-synuclein aggregation.

α-Synuclein forms amyloid deposits in the dopaminergic neurons; a process that is believed to contribute to the Parkinson's disease. An emerging theme in amyloid research is the hypothesis that the toxic species produced during amyloid formation share common physic-chemical features and exert their effects by common modes. This prompted the idea that molecules able to inhibit a protein aggregation process may cross-react with other amyloidogenic proteins, interfering in their fibrils formation.

Ceftriaxone blocks the polymerization of α-synuclein and exerts neuroprotective effects in vitro.

The β-lactam antibiotic ceftriaxone was suggested as a therapeutic agent in several neurodegenerative disorders, either for its ability to counteract glutamate-mediated toxicity, as in cerebral ischemia, or for its ability to enhance the degradation of misfolded proteins, as in Alexander's disease. Recently, the efficacy of ceftriaxone in neuroprotection of dopaminergic neurons in a rat model of Parkinson's disease was documented. However, which characteristics of ceftriaxone mediate its therapeutic effects remains unclear.

Small molecules interacting with α-synuclein: antiaggregating and cytoprotective properties.

Curcumin, a dietary polyphenol, has shown a potential to act on the symptoms of neurodegenerative disorders, including Alzheimer's and Parkinson's diseases, as a consequence of its antioxidant, anti-inflammatory and anti-protein aggregation properties. Unfortunately, curcumin undergoes rapid degradation at physiological pH into ferulic acid, vanillin and dehydrozingerone, making it an unlikely drug candidate. Here, we evaluated the ability of some curcumin by-products: dehydrozingerone (1), its O-methyl derivative (2), zingerone (3), and their biphenyl analogues (4-6) to interact with α-synuclein (AS), using CD and fluorescence spectroscopy.

Peptide-receptor ligands and multivalent approach.

The overexpression of peptide receptors in human tumours makes peptide-ligands attractive agents for the development of specific diagnostic imaging and/or therapy of cancers. Solid-phase peptide synthesis, modern phage display technology and combinatorial peptide chemistry have profoundly affected the pool of available targeting peptides for efficient and specific delivery of imaging or therapeutic label molecules. Additionally, the availability of a wide range of bifunctional chelating agents for the radiolabelling of bioactive peptides with radionuclides has produced a wide variety of useful radiopharmaceutical molecules.

Cell-Penetrating Peptides: A Comparative Study on Lipid Affinity and Cargo Delivery Properties.

A growing number of natural and/or synthetic peptides with cell membrane penetrating capability have been identified and described in the past years. These molecules have been considered promising tools for delivering bioactive compounds into various cell types. Although the mechanism of uptake is still unclear, it is reasonable to assume that the relative contribute of each proposed mechanism could differ for the same peptide, depending on experimental protocol and cargo molecule composition.