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. Methods: 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.

Beneficial effects of choline alphoscerate on amyloid-β neurotoxicity in an in vitro model of alzheimer’s disease

Burgaletto C.;Di Benedetto G.;Bernardini R.;Cantarella G.
2021

Abstract

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. Methods: 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.
Acetylcholine
Alzheimer’s disease
Apoptosis
Cholinergic neurotransmission
Neurons
Synaptogenesis
Alzheimer Disease
Amyloid beta-Peptides
Animals
Cell Differentiation
Glycerylphosphorylcholine
Humans
In Vitro Techniques
Mice
Neurons
Peptide Fragments
Phosphorylation
tau Proteins
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11769/522602
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