Beneficial Effects of Choline Alphoscerate on Amyloid-β Neurotoxicity in an In vitro Model of Alzheimer’s Disease

Background: Alzheimer’s disease (AD) is the most common form of neurodegenerative disorder characterized by cognitive impairment, which represents an urgent public health concern. Given the worldwide impact of AD, there is a compelling need for effective therapies to slow down or halt this disorder. Objective: Choline alphoscerate (α-GPC) represents a potentially effective cholinergic neurotrans- mission enhancing agent with an interesting clinical profile in cognitive dysfunctions improve- ment, although only scanty data are available about the mechanisms underlying such beneficial ef- fects. Method: The SH-SY5Y neuronal cell line, differentiated for 1 week with 10 μm of all-trans-reti- noic acid (RA), to achieve a switch towards a cholinergic phenotype, was used as an in vitro model of AD. SH-SY5Y cells were pre-treated for 1h with α-GPC (100nM) and treated for 72 h with Aβ25-35 (10μM). Results: α-GPC was able to antagonize Aβ25-35 mediated neurotoxicity and attenuate the Aβ-in- duced phosphorylation of the Tau protein. Moreover, α-GPC exerted its beneficial effects by em- ploying the NGF/TrkA system, knocked down in AD and, consequently, by sustaining the expres- sion level of synaptic vesicle proteins, such as synaptophysin. Conclusion: Taken together, our data suggest that α-GPC can have a role in neuroprotection in the course of toxic challenges with Aβ. Thus, a deeper understanding of the mechanism underlying its beneficial effect, could provide new insights into potential future pharmacological applications of its functional cholinergic enhancement, with the aim to mitigate AD and could represent the basis for innovative therapy.

Increased Levels of Lipid Oxidation Products in Rheumatically Destructed Bones o f Patients Suffering from Rheumatoid Arthritis

The new indicator for lipid peroxidation (LPO) processes -9-hydroxy-10,12-octadecadie-noic acid (9-HODE) -was used to investigate, whether LPO processes are increased in destructed bone material of patients suffering from rheum atoid arthritis (RA) in comparison to surrounded non destructed bone material. The HODE content in destructed bones ex­ceeded that of non destructed ones of the same patient for a factor of about 3. In addition similar increases in leukotoxines and epoxy oleic acid in the destructed bone material were observed, indicating an increase of LPO processes in affected bone parts of pa­tients.

Direct Release of Ethylene from Methionine and Methionine Containing Peptides by Action of 13-Hydroperoxy-(9cis, 11trans)-octadecadienoic Acid

13-Hydroperoxy-9cis,12trans-octadecadienoic acid (13-LOOH) reacts with methionine and methionine-containing peptides in absence of any other reagent by slow release of ethylene. Ethylene was identified by mass spectrometry and quantified by gas chromatography. The amount of ethylene released in a certain time interval depends on the position of the methionine residue in the peptide chain. Highest rates of ethylene release were measured with peptides carrying methionine at the N-terminus. 13-Hydroperoxy-9cis,12trans-octadecadie-noic acid can be substituted by linoleic acid, lipoxigenase and oxygen. We assume that the instant formation of lipid peroxides after plant injury and the instant release of ′wound ethylene′ are related. Since the initiator tRNA in eucaryontic cells always carries a methionine, all newly produced proteins contain methionine at the N-terminal position and are therefore sensitive to oxidative damage by hydroperoxides of fatty acids.