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Global Translational Medicine Traumatic memories in PTSD

encode memories in a quantum manner through calcium– Studies have demonstrated that MLR, an oral
calmodulin-dependent protein kinase II (CaMKII). 90 supplementation with natural phospholipids and antioxidants,
Recent pre-clinical studies showed that social stress halts the dissemination of cellular senescence to neighboring
disrupts memory by impairing tubulin polymerization, healthy cells by inhibiting SASP. 101-103 (Figure 1). Furthermore,
thereby linking traumatic amnesia and hypermnesia, MLR facilitates not only cell membranes but also the damaged
documented in PTSD, to microtubular pathology. 91,92 mitochondrial inner and outer membranes with natural lipid
PTSD-related intrusive memories may depend on the species. In fact, the loss of lysophosphatidylethanolamine
degree of tau phosphorylation. (LPE), phosphatidylglycerol (PG), and phosphatidylinositol
(PI) in senescent mitochondria causes organelle death.
Under physiological conditions, GSK-3β phosphorylates Conversely, replacement with healthy lipids may promote
tau protein, stabilizing the conformation of MTs. mitochondrial homeostasis. 26
Nevertheless, excessive tau phosphorylation destabilizes
MTs, altering not only recall but also behavior. 38,93 5.2. Phosphoinositide-dependent kinase 1 (PDK-1)
MT-destabilizing agents, including chemotherapeutics, inhibitors
colchicine, and fluorides, are associated with defective In contrast to the long-held belief that cellular senescence
recall and behavioral disturbances. 94,95 Because the same and proliferation arrest are irreversible, groundbreaking
agents activate microglia, it is not surprising that these cells data now suggest a promising avenue for intervention.
have been implicated in behavioral disturbances. 96 PDK-1 inhibitors, particularly kaempferol, can potentially
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Recent research has demonstrated that the tau protein reverse the senescent phenotype. This discovery
engages in brain oscillatory activity, contributing to opens up new possibilities for research and treatment in
the rapid oscillations implicated in higher cognitive biochemistry, pharmacology, and neurology. Furthermore,
functions. 97 combining PDK-1 inhibitors with MLR and berberine
may offer a novel approach to antipsychotic treatment
Altogether, under pathological conditions, GSK-3β that avoids the typical adverse effects associated with
may engage in the hyperphosphorylation of tau protein, conventional antipsychotics.
thereby maintaining traumatic memories and fear.
5.3. Kaempferol
5. Therapeutic strategies
Kaempferol is a flavonoid that reduces lipid peroxidation
We had previously discussed potential novel therapies for and directly inhibits GSK-3β. It also exhibits
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PTSD. 26,98 Here, we describe a unique strategy, membrane antimicrobial, anti-inflammatory, antioxidant, antitumor,
lipid replacement (MLR) augmented with kaempferol cardioprotective, neuroprotective, and antidiabetic
and berberine. This combination of natural compounds activities. Due to GSK-3β inhibition, the effects of
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suppresses GSK-3β activity through three distinct kaempferol are similar to those of lithium and several
mechanisms, thus averting tau hyperphosphorylation. antipsychotics, indicating its probable efficacy against
psychosis and mood instability without the side effects of
5.1. Membrane lipid replacement conventional psychotropic drugs (Figure 1).
MLR is a technique that utilizes healthy, natural Kaempferol possesses antioxidant properties and scavenges
glycerophospholipids to substitute the oxidized reactive oxygen species. It also deactivates the nuclear factor
components of the plasma membrane lipid bilayer, kappa-light-chain-enhancer of activated B cell (NF-κB)
thus restoring the physiological fluidity of the cell and signaling, indicating anti-inflammatory properties and the
mitochondrial membranes. The membrane lipid bilayer ability to reduce neuroinflammation as shown in Table 1.
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comprises phospholipids, cholesterol, and ceramide, which
disrupt neurotransmission when oxidized. Oxidized lipids, 5.4. Berberine
including oxysterols, phospholipids, and toxic ceramide, Berberine is a plant alkaloid extracted from Hydrastis
are gradually replaced with natural glycerophospholipids, canadensis, Phellodendron chinense, Coptis chinensis, and
restoring membrane homeostasis.
Berberis aquifolium. It has been used in Asia for centuries
A subclass of glycerophospholipids are plasmalogens, due to its antimicrobial and antihelminthic properties.
lipids containing a vinyl-ether bond that comprises Berberine has been used to treat CVD, hyperlipidemia,
up to 20% of the total membrane lipid. Plasmalogen diabetes, and hypertension as it reduces toxic levels
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levels may decrease in the brain tissue of patients with of ceramide, lowering the insulin resistance caused by
AD, suggesting that plasmalogen supplementation is this toxin. Furthermore, berberine recently received
beneficial. 100 attention as a potential anticancer agent, a property

Volume 3 Issue 4 (2024) 6 doi: 10.36922/gtm.3974