Recent Developments in Protein Lactylation in PTSD and CVD: Novel Strategies and Targets
Abstract
:1. Introduction
2. Human Stress Response: A Quick Reminder
3. Protein Lactylation, the Warburg Effect 2.0
3.1. Virus-Induced PTSD and CVD
3.2. Virus-Induced Senescence (VIS)
4. From Cellular to Organismal Stress
5. The Mystery of ERAP2
- A recombinant ERAP2 may be beneficial for the treatment of PTSD and CVD;
- ERAP2 may be a viable marker for PTSD vulnerability.
6. Potential Interventions
6.1. OXT
6.2. HIF-1α
6.3. ASIC1 Blockers
- -
- -
- C5B, a synthetic ASIC1 inhibitor, crosses the BBB and protects against neuronal apoptosis, indicating potential benefits for PTSD and CVD [216].
- -
- -
6.4. Lactylation
- -
- -
- Oxamate has been found helpful for both CVD and psychological stress, indicating potential PTSD benefits [232].
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- Quinoline 3-sulfonamides, is a novel LDH inhibitor that reverses aerobic glycolysis in cancer cells, and various quinoline derivatives have been tested as anticancer agents [233,234]. Quinolines have been known for their antidepressant and antipsychotic properties, as aripiprazole is derived from these compounds [235]. Several studies have demonstrated the beneficial effect of aripiprazole on PTSD, suggesting that these drugs should be further interrogated [236,237].
- -
- Galloflavin is a newer LDH inhibitor that, to our knowledge, has not been assessed for CVD or PTSD, but its pharmacological profile suggests potential efficacy.
6.5. Interleukin 7
6.6. Autophagy and UPR
6.7. Significance for the Field and Novel Targets
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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IL-7 Signaling | PTSD/CVD | References (Adapted from) |
Upregulate Warburg effect | Upregulate Warburg effect | [153] |
Lower SARS-CoV-2 risk | Higher SARS-CoV-2 risk | [154,155,156] |
Thymic activation | Thymic autophagy | [65,157] |
Upregulated autophagy | Downregulated autophagy | [158,159,160,161] |
Lower endothelial/immune senescence | Increased endothelial/immune senescence | [44,162] |
Therapeutic Agent | Mechanism | References (Adapted from) |
OXT | ||
Intranasal OXT | Substitution therapy | |
Lactobacillus reuteri | Synthesizes OXT | [196,197] |
HIF-1α | ||
Intermittent hypoxia | Upregulates HIF-1α | [8,9,10] |
Hyperbaric oxygen | Lowers hypoxia | [11,12,13,14,15,16] |
A2B blockers | ||
PSB-603 | Decrease obesity and aging | [203,204] |
ASIC blockers | ||
Amyloride | Potassium-sparing diuretic | [214,215] |
C5B | Neuroprotective | [216] |
Sevanol | ASIC1 and ASIC3 inhibitor | [219,220] |
Epigallocatechin gallate | ASIC3 inhibitor | |
LDH inhibitors | ||
5-ALA | Improves mood, fatigue, sleep | [229,230,231] |
Quinoline 3-sulfonamides | Reverses glycolysis | [233,234] |
Galloflavin | Inhibits lactate production; decreases ATP synthesis | [217] |
Autophagy activators | ||
Antidepressants/ketamine | Increase autophagic markers LC3II/I | [242,243,244,245] |
Recombinant ERAP2 | Lower ER stress | [246] |
Lactylation inhibitors | ||
Demethylzeylasteral (DML) | Lowers depression, atherosclerosis, pain | [238] |
IL-7 | ||
IL-7 recombinant GX-17 | Prevents cellular senescence | [247,248] |
Thymic activators | ||
Photobiomodulation | Restores thymic function | [67] |
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Kozlakidis, Z.; Shi, P.; Abarbanel, G.; Klein, C.; Sfera, A. Recent Developments in Protein Lactylation in PTSD and CVD: Novel Strategies and Targets. BioTech 2023, 12, 38. https://doi.org/10.3390/biotech12020038
Kozlakidis Z, Shi P, Abarbanel G, Klein C, Sfera A. Recent Developments in Protein Lactylation in PTSD and CVD: Novel Strategies and Targets. BioTech. 2023; 12(2):38. https://doi.org/10.3390/biotech12020038
Chicago/Turabian StyleKozlakidis, Zisis, Patricia Shi, Ganna Abarbanel, Carolina Klein, and Adonis Sfera. 2023. "Recent Developments in Protein Lactylation in PTSD and CVD: Novel Strategies and Targets" BioTech 12, no. 2: 38. https://doi.org/10.3390/biotech12020038
APA StyleKozlakidis, Z., Shi, P., Abarbanel, G., Klein, C., & Sfera, A. (2023). Recent Developments in Protein Lactylation in PTSD and CVD: Novel Strategies and Targets. BioTech, 12(2), 38. https://doi.org/10.3390/biotech12020038