Title:Beneficial Effects of Choline Alphoscerate on Amyloid-β Neurotoxicity in an In vitro Model of Alzheimer’s Disease
Volume: 18
Issue: 4
关键词:
乙酰胆碱、细胞凋亡、胆碱能神经传递、神经元、突触发生、阿尔茨海默病。
摘要:
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 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 μm 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 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-induced
phosphorylation of the Tau protein. Moreover, α-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 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.