Beneficial Effects Of Choline Alphoscerate On Amyloid-Beta 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 (alpha-GPC) represents a potentially effective cholinergic neurotransmission enhancing agent with an interesting clinical profile in cognitive dysfunctions improvement, although only scanty data are available about the mechanisms underlying such beneficial effects. Methods: The SH-SY5Y neuronal cell line, differentiated for 1 week with 10 mu m of all-trans-retinoic 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 alpha-GPC (100nM) and treated for 72 h with A beta 25-35 (10 mu M). Results: alpha-GPC was able to antagonize A beta 25-35 mediated neurotoxicity and attenuate the A beta-induced phosphorylation of the Tau protein. Moreover, alpha-GPC exerted its beneficial effects by employing the NGF/TrkA system, knocked down in AD and, consequently, by sustaining the expression level of synaptic vesicle proteins, such as synaptophysin. Conclusion: Taken together, our data suggest that alpha-GPC can have a role in neuroprotection in the course of toxic challenges with A beta. 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.