Figure 2. Illustration of the cellular and molecular targets of total and individual Panax notoginseng saponins (PNS) on neural cells destroyed by Alzheimer's disease. (1) Prevention of Aβ formation and Amelioration of Aβ cytotoxicity. In the non-amyloidogenic pathway, α-secretase (α-sec) cleaves amyloid precursor protein (APP) within the Aβ domain, therefore precludes the formation of Aβ. In the amyloidogenic pathway, β-secretase (β-sec) and γ-secretase cleaves APP to produce Aβ. (2). Reduction of intracellular calcium overload. Increased calcium entered cells via the voltage-gated calcium channel currents (VGCC), resulting in calcium overload. (3) Regulation of Tau protein phosphorylation. In AD, there is a reduction in the ability of Tau to bind to tubulin and promote microtubule assembly. Hyperphosphorylated Tau contributes to the destabilization of microtubules and ultimately the formation of neurofibrillary tangle (NFT). (4) Increasing the activation of the cholinergic nervous system. Acetylcholine (ACh) is synthesized in the cytosol of cholinergic presynaptic neurons from choline and acetyl-coenzyme A (acetyl-CoA) by the enzyme choline acetyltransferase (ChAT) and is then transferred into synaptic vesicles. In the synaptic cleft, ACh is rapidly hydrolyzed by the enzyme acetylcholinesterase (AChE), releasing acetate and choline. Red arrow, promotion; green arrow, inhibition.
