Na⁺‐K⁺‐ATPase, a potent neuroprotective modulator against Alzheimer disease

Abstract

Alzheimer disease (AD) is a neurodegenerative disorder clinically characterized by progressive cognitive and memory dysfunction, which is the most common form of dementia. Although the pathogenesis of neuronal injury in AD is not clear, recent evidences suggest that Na⁺-K⁺-ATPase plays an important role in AD, and may be a potent neuroprotective modulator against AD. This review aims to provide readers with an in-depth understanding of Na⁺-K⁺-ATPase in AD through these modulations of some factors that are as follows, which leads to the change of learning and memory in the process of AD. 1. The deficiency in Na⁺, K⁺-ATPase α1, α2 and α3 isoform genes induced learning and memory deficits, and α isoform was evidently changed in AD, revealing that Na⁺, K⁺-ATPase α isoform genes may play an important role in AD. 2. Some factors, such as β-amyloid, cholinergic and oxidative stress, can modulate learning and memory in AD through the mondulation of Na⁺-K⁺-ATPase activity. 3. Some substances, such as Zn, s-Ethyl cysteine, s-propyl cysteine, citicoline, rivastigmine, Vit E, memantine, tea polyphenol, curcumin, caffeine, Alpinia galanga (L.) fractions, and Bacopa monnieri could play a role in improving memory performance and exert protective effects against AD by increasing expression or activity of Na⁺, K⁺-ATPase.

Astrocytic transporters in Alzheimer's disease

“…Most recently, the α3 neuronal specific Na + .K + -ATPase isoform is a target for Aβ assemblies, presenting a potential novel therapeutic strategy (207). (209)(210)(211). This has led to an increasing number of Na + .K + -ATPase modulators being proposed as AD therapeutics (211).…”

“…(209)(210)(211). This has led to an increasing number of Na + .K + -ATPase modulators being proposed as AD therapeutics (211). Many of these are preclinical observations tested in expression systems that remain to be robustly tested, of note however is the observation that currently approved AD therapeutics rivastigmine and memantine have been reported to increase Na + .K + -ATPase activity (212,213).…”

Phosphorylation of the Amyloid-Beta Peptide Inhibits Zinc-Dependent Aggregation, Prevents Na,K-ATPase Inhibition, and Reduces Cerebral Plaque Deposition

“…By contrast, phosphorylation at Ser8 may change the interaction of Aβ with other proteins, such as Na + ,K + -ATPase. Previously, it was shown that Na + ,K + -ATPase activity was inhibited in post-mortem tissues of AD patients and in amyloid-containing hippocampi of transgenic mice (but not in the amyloid-free cerebellum) (Dickey et al, 2005; Kreutz et al, 2013; Zhang et al, 2013). The latest studies demonstrated that Aβ 42 in form of monomers or oligomers directly binds to Na + ,K + -ATPase, which results in the inhibition of the enzyme as well as the triggering of intracellular signaling cascades (Ohnishi et al, 2015; Petrushanko et al, 2016).…”

Functional proteomics of synaptic plasma membrane ATP-ases of rat hippocampus: Effect of l-acetylcarnitine and relationships with Dementia and Depression pathophysiology

“…This evidence prompted Zhang et al (2013) to state that "substances enhancing Na þ , K þ -ATP-ase activity may improve symptoms and/or delay disease progression, and be potent neuroprotective agents against AD". Actually, Amyloid β (Aβ) directly decreases Na þ -K þ -ATP-ase activity, and the disruption of ion homeostasis may interfere with normal electronic properties of dendrites, contributing to neuritic dystrophia and memory dysfunction.…”