Energy, could be the future therapeutic modalities? Abdelrazak Mansour Ali 1 *, and Ahmed Abdelrazak Ali 2,
Energy, could be the future therapeutic modalities?
Abdelrazak Mansour Ali 1 *, and Ahmed Abdelrazak Ali 2,
1*. Al-Azhar University affiliated, Faculty of Medicine, Pediatrics Department, Cairo, Egypt. Email; [email protected].
2.Virginia Commonwealth University affiliated, Information system Department. USA.
?
Abstract. In contrast to the common impression that exposure to a magnetic field of low frequency causes mutations to organisms, we have demonstrated that a magnetic field can enhance and improve the efficiency of DNA repair. The improvement was found to be mediated by the induced overproduction of heat shock proteins Dna K/J (Hsp70/40). The exposure of 900 MHz RF at 120 μW/cm2?power flux density could increase ROS level and activate a transient UPRmt?in in response to mitochondria stress, increasing the expression of HSP10/HSP60/ClpP proteins, restoring mitochondrial homeostasis. some molecules interact through electromagnetic waves instead of direct contact. Recent data indicate that kinases activated by heat shock can regulate synthesis and functioning of the molecular chaperones, and these chaperones modulate activity of the cell death and survival pathways. Many members of this group perform?chaperone?functions by stabilizing new proteins to ensure correct folding or by helping to refold proteins that were damaged by the cell stress. Fusion proteins with chaperone components have been employed for increased efficiency of recombinant protein production. These chaperone proteins also increased in expression as a response to heat shock, hence their label as heat shock proteins (Hsps). Transcranial Electromagnetic Treatment (TEMT) appears to be safe. It disaggregates both Aβ and p-tau oligomers and induces brain mitochondrial enhancement. Thus, prevent and reverse memory impairment in AD.?Stress-induced cell protecting heat shock proteins (HSP) have been considered as a potential treatment target for autoimmune diseases. Mitochondrial cholesterol is a new concept of therapies targeted to boosting mitochondrial antioxidant and may be a promising approach for the treatment of diseases that share mitochondrial cholesterol imbalance as a common hallmark.
Discussion. In contrast to the common impression that exposure to a magnetic field of low frequency causes mutations to organisms, we have demonstrated that a magnetic field can enhance and improve the efficiency of DNA repair. The improvement was found to be mediated by the induced overproduction of heat shock proteins Dna K/J (Hsp70/40) [1].
?Interestingly, there is a growing body of literature describing positive effects of an EM field on mitochondria. A study has shown that application of a low intensity constant EM field source on osteogenic cells in vitro resulted in increased mitochondrial membrane potential and respiratory complex I activity and induced osteogenic differentiation. In the presence of mitochondrial inhibitor antimycin A, the osteo inductive effect was reversed, confirming that this effect was mediated via increased Ox Phos activity [2]. The DNA molecule is considered as an object of nature-like technologies, with the focus on the special electromagnetic properties of DNA-like helices. DNA-like helices are regarded as artificial micro-resonators, or “meta-atoms,” exhibiting both dielectric and magnetic properties, that are equally pronounced. Methods for creating spatial structures directly from DNA molecules, as well as from DNA-like helices were presented. It is shown that the design of metamaterials and Meta surfaces should be carried out considering the special electromagnetic properties of DNA-like helices. This will make it possible to obtain the required properties of metamaterials and Meta surfaces and achieve advantages over other types of artificial structures [3]. Mitochondrial homeostasis determined the fate of cells. The functioning of the mitochondria is in turn tightly aligned to energy transduction and to the control of calcium and redox stress homeostasis [4]. The exposure of 900 MHz RF at 120 μW/cm2?power flux density could increase ROS level and activate a transient UPRmt?in in response to mitochondria stress, increasing the expression of HSP10/HSP60/ClpP proteins, restoring mitochondrial homeostasis. Mitochondrial homeostasis in term of protein folding ability is restored 24 h post-RF exposure. Exposure to RF in experimental condition did not cause permanent and severe mitochondrial dysfunctions. However, the detailed underlying molecular mechanism of RF-induced UPRmt?remains to be further studied [5].
The rotation and vibrational energy levels of biomacromolecules fall in the energy range of terahertz waves; thus, terahertz waves might interact with biomacromolecules. Therefore, terahertz waves have been widely applied to explore features of the terahertz spectrum of biomacromolecules.?The interaction between terahertz and biomacromolecules is very important. To date, we have found that different biomacromolecules have different absorption peaks. However, no complete spectral analysis of biomacromolecules has been established. In addition, terahertz waves can cause structural changes in some biological macromolecules, but the frequency range has not been clarified, and the ultimate function of organisms has not been explained [6]. ?terahertz radiation begins at a wavelength of around 1?millimeter and proceeds into shorter wavelengths, it is sometimes known as the?submillimeter band, and its radiation as?submillimeter waves. This band of electromagnetic radiation lies within the transition region between?microwave?and?far infrared and can be regarded as either.
Terahertz radiation is strongly?absorbed?by the?gases?of the?atmosphere, and in air is?attenuated?to zero within a few meters [7,8].?So, it is not practical for terrestrial?radio communication. It can penetrate thin layers of materials but is blocked by thicker objects. THz beams transmitted through materials can be used for?material characterization, layer inspection, relief measurement [9]?and as a lower-energy alternative to?X-rays?for producing high resolution images of the interior of solid objects [10]
It is proposed by Montagnier [11] that some molecules interact through electromagnetic waves instead of direct contact. These waves could be trapped into coherence domains formed by water molecules vacuum spheres at quantum scales. These structures would keep the signal in the absence of the original molecule. During the PRC step of the experiment, this remaining signal could have contained the necessary information for the initial DNA to be reconstructed.
The principle is like Benvenuto’s experiment from 1997 [12]. where EMS was recorded from ovalbumin at the Northwestern University Medical School of Chicago and transmitted through email to Benvenuto’s Digital Biology Laboratory in Clamart, France. After emitting the signal on pure water for 20 minutes, the water could cause an allergic shock on an isolated Guinea-pig heart allergic to ovalbumin. In both experiments the EMS reproduces the properties of the original molecules in their absence.
One of the EMS types is the potential vortex which has significant characteristics. With its concentration effect, it provides for miniaturization down to a few nanometers, which allows enormously high information density in the nucleus. With this first introduction of the magnetic scalar wave, it becomes clear that this wave is suitable to use genetic code chemically stored in the base pairs of the genes and electrically modulate them, to "piggyback" information from the cell nucleus to another cell. At the receiving end, the reverse process takes place, and the transported information is converted back into a chemical structure. The necessary energy required to power the chemical process is provided by the magnetic scalar wave itself [13].
Heat shock proteins?(HSP) are a family of?proteins?produced by?cells?in response to exposure to?stressful?conditions. They were first described in relation to?heat shock [14].?but are now known to also be expressed during other stresses including exposure to cold [15].?UV light [16].?and during wound healing or tissue remodeling [17].?Many members of this group perform?chaperone?functions by stabilizing new proteins to ensure correct folding or by helping to refold proteins that were damaged by the cell stress [18].?This increase in expression is?transcriptionally?regulated. The dramatic?upregulation?of the heat shock proteins is a key part of the?heat shock response?and is induced primarily by?heat shock factor?(HSF) [19].?HSPs are found in virtually all living organisms, from?bacteria?to?humans. Considering the dense population of the cytosol (average protein conc: 150 mg/mL), Finka and Goloubinoff [20] proposed an inherent need to protect nascent polypeptides from “unwanted associations” that prevent the attainment of the functional protein fold. Expression of these proteins was increased with heat shock treatment, leading to their label as heat shock proteins ‘Hsps’ [21]. Heat shock of mammalian cells causes protein damage and activates several signaling pathways. Some of these pathways enhance the ability of cells to survive heat shock, e.g., induction of molecular chaperones [heat shock protein (HSP) HSP72 and HSP27], activation of the protein kinases. Recent data indicate that kinases activated by heat shock can regulate synthesis and functioning of the molecular chaperones, and these chaperones modulate activity of the cell death and survival pathways. Therefore, the overall balance of the pathways and their interplay determine whether a cell exposed to heat shock will die or survive and become stress tolerant [22]. Structural analysis allows us to associate features of the chaperone proteins to their different functional domains. Perhaps the best application of this is for the construction of fusion proteins with combined features of different selected chaperones. Some of these chaperones have been documented to work in cooperation (e.g., Hsp70 and Hsp90; [23]). Fusion proteins with chaperone components have been employed for increased efficiency of recombinant protein production [24]. The proteins’ ability to prevent unwanted associations led to their being called chaperones. These chaperone proteins also increased in expression as a response to heat shock, hence their label as heat shock proteins (Hsps). The term “unfoldases” has been proposed, as this basic function is shared by most members of this protein family [25].
Therapeutic applications.
Transcranial Electromagnetic Treatment (TEMT) disaggregates both Aβ and p-tau oligomers and induces brain mitochondrial enhancement. These apparent “disease-modifying” actions of TEMT both prevent and reverse memory impairment in AD.?TEMT administration to AD subjects appears to be safe, while providing cognitive enhancement, changes to CSF/blood AD markers, and evidence of stable/enhanced brain connectivity [26]. REMFS to influence various networks within known biological systems dysregulated in AD. The potential implications of REMFS as a therapeutic modality are likely to be far in the future, but the ability of RF-EMF to significantly reduce Aβ40 and Aβ42 levels in human neurons, coupled with animal model results, indicate a pathway worth further exploration. These results in cell and animal systems are likely achieved through a combination of efficient Aβ degradation, autophagy-lysosome system [27], and proteasome system activation [28], as well as the reduction of β-secretase activity [29]. Yet, we must note that quantum tunneling-based model could explain the conformational changes of molecules involved in other biological pathways not mentioned here.
The proposed quantum tunneling mechanism is the first to provide an explanation of how low energy radio-frequency radiation may induce a biological response. Quantum tunneling allows for an understanding of events occurring between single photons and biomolecules that would otherwise be extremely difficult to visualize in experimental studies. Hence, it is by way of quantum tunneling that we finally understand the intimate relationship between REMFS and the HBN?(hexagonal boron nitride) of the interfacial water of biomolecules. The process is a time dependent adiabatic perturbation of the HBN that is set into motion as a photon carried along an EM wave (with a frequency lower than the H bond frequency) that forces the H bond to change its frequency to that of the EM wave, thereby increasing the amplitude of the H bond vibrations in a process like a driven quantum oscillator [30]. The increased amplitude will decrease the H bond donor–acceptor distance and result in an increased probability of proton tunneling [31]. Consequently, interfacial water will donate its hydrogen toward protonation of nucleic acids, and the tautomeric interconversions that ensue result in structural changes in biomolecules and RNA, namely HSR1. The secondary structure produced will then bind to HSF1 and cause its dissociation from the multi-chaperone complex, freeing it from inhibition. Once activated, the HSF1 monomer undergoes trimerization and accumulation, inducing the expression of Hsp70 and thereby activating Aβ-clearance pathways to delay cellular senescence [32].
Autoimmune therapy. The self-reactivity of heat shock proteins protects host against disease by controlling induction and release of pro-inflammatory cytokines. However, antibodies to self-heat shock proteins haven been implicated in pathogenesis of autoimmune diseases like arthritis and atherosclerosis. Some heat shock proteins are potent inducers of innate and adaptive immunity. They activate dendritic cells and natural killer cells through toll-like receptors, CD14 and CD91. They play an important role in MHC-antigen processing and presentation. These immune effector functions of heat shock proteins are being exploited them as therapeutic agents as well as therapeutic targets for various infectious diseases and cancers [33]. Autoimmune therapy remains challenging and consists of conventional immunosuppressive treatments, including corticosteroids and more advanced biological therapies which are targeted at molecules involved in maintaining chronic inflammation. These therapies are focused on suppressing inflammation; nevertheless, a permanent balance between protective and pathogenic immune responses is not achieved. In addition, most of currently available therapies for autoimmune diseases induce severe side effects. Consequently, more effective, and safer therapies are still required to control autoimmunity. Stress-induced cell protecting heat shock proteins (HSP) have been considered as a potential treatment target for autoimmune diseases. HSP, predominantly intracellular components, might be released from bacteria or mammalian tissues and activate immune response. This activation may lead to either production of (auto)antibodies against HSP and/or induction of immune regulatory mechanisms, including expansion of desired T regulatory (Treg) cells. Because inadequate frequency or activity of Treg is a characteristic feature of autoimmune diseases, targeting this cell population is an important focus of immunotherapy approaches in autoimmunity [34].
As the protein homeostasis is important for cell integrity, survival and metabolism, impairment of chaperone‐assisted protein quality control leads to the onset and development of various diseases.
At the same time, although a lot of studies have proved that HSPs play an important role in the development of diseases, the current drug development for HSPs is not fulfilled. Many HSP90 inhibitors in clinical trials were terminated or delayed due to toxicity or lack of efficacy [35]. It has observed that the use of HSP90 inhibitors could lead to the activation of HSF1, which, in turn, induce the activation of other HSPs to overcome the lack of HSP90. Therefore, development of inhibitors against multiple HSPs or HSF1 may be a strategy to enhance the efficacy of HSP90 inhibitors and overcome the HSF1‐mediated feedback. In the meantime, we also need to pay attention to the safety of these inhibitors in use. Better understanding of how HSPs function in vivo and the collaboration between the HSPs in cancers will be crucial for reducing toxicity to normal cells and a more accurate indication selection [36]. ?
Mitochondrial role.?Due to the critical role of cholesterol in cell physiology and function, alterations in cholesterol homeostasis and metabolism have been linked to a myriad of pathological conditions. Here, rather than analyzing the role of total cholesterol levels, we focus on understanding how the intracellular cholesterol pools, particularly in mitochondria, influence metabolism and redox biology and trigger the onset of prevalent liver diseases, such as NAFLD, NASH or HCC, as well as neurodegenerative diseases like AD and NPC disease. Although the pathogenesis of these disorders is different, increased accumulation of cholesterol in mitochondria, which exceeds its metabolism, emerges as a common denominator in all of them [37,38,39]. One important conclusion we extracted from our studies is that the accumulation of cholesterol in mitochondrial membranes exerts similar effects despite the affected organ or disease's etiology. Cholesterol overload impairs the transport of GSH from the cytosol to the mitochondrial matrix, rendering brain mitochondria more susceptible to Aβ-induced ROS generation and neurotoxicity, while in the liver, in addition to the oxidative damage coming from excess ROS formation, it promotes BAs production in the mitochondrial acidic pathway and enhances hepatic tumorigenesis. Thus, based on these findings, mitochondrial cholesterol may emerge as a new concept of study and therapies targeted to boosting mitochondrial antioxidant armamentarium may be a promising approach for the treatment of diseases that share mitochondrial cholesterol imbalance as a common hallmark [40]. Increased mitochondrial cholesterol levels have been observed in diverse pathological conditions including cancer, steatohepatitis, Alzheimer disease and Niemann-Pick Type C1-deficiency. [41], and Inflammatory Bowel Disease, highlighting the therapeutic potential of dietary phytochemicals, restoring intestinal metabolism and function [42]. Mitochondrial therapy may have a place in the treatment of a diverse array of disorders, including neurodegenerative diseases, ischemic stroke, and TBI. Transplantation of mitochondria is likely to offer a means to mitigate damage to diseased or injured brain and refinement of techniques for delivery warrants further study. [43]. A study suggested genomic MitoG228A has potential to be used as a risk factor in the clinic and as a target for therapeutics [44]. Compound 29 (full name, 5-cholesten-3beta,25-diol), also known as VP1-001 (Viewpoint Therapeutics) and as 25-hydroxy-cholesterol, is an oxysterol, a derivative of cholesterol. Usha Andley, “PhD, FARVO”, is an investigator conducting research on this chemical compound’s use as a treatment for cataracts [45,46]. compound 29 is found to be a successful, it may not only lead to new treatments for cataracts; it could also open the door to new treatments for other conditions involving amyloid proteins, such as?Alzheimer’s disease [47].
Conclusion. Stress-induced cell protecting heat shock proteins (HSP) have been considered as a potential treatment target for autoimmune diseases. The exposure of 900 MHz RF at 120 μW/cm2?power flux density could increase ROS level and activate a transient UPRmt?in in response to mitochondria stress, increasing the expression of HSP10/HSP60/ClpP proteins, restoring mitochondrial homeostasis. Recent data indicate that kinases activated by heat shock can regulate synthesis and functioning of the molecular chaperones, stabilizing new proteins to ensure correct folding or by helping to refold proteins that were damaged by the cell stress Mitochondrial therapy may have a place in the treatment of a diverse array of disorders, including neurodegenerative diseases, ischemic stroke, and TBI. Transplantation of mitochondria is likely to offer a means to mitigate damage to diseased or injured brain and refinement of techniques for delivery warrants further study.
Abbreviations.
NAFLD = non-alcoholic fatty liver disease
NASH = non-alcoholic steatohepatitis
HCC = hepatocellular carcinoma
TBI = traumatic brain injury.
NPC = Niemann-Pick Type C.
Compliance with ethical standards
Acknowledgments. We thank Shehab Ali, the expert in computer science, and the researcher Radwa Ali, for their discussions and help to this study.
Disclosure of conflict of interest. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare no conflict of interest.
No funds received from any individuals or organizations for any step of this study.
?
References
1- Chow K, Tung WL. Magnetic field exposure enhances DNA repair through the induction of DNA K/J synthesis. FEBS Lett. 2000 Jul 28;478(1-2):133-6. doi: 10.1016/s0014-5793(00)01822-6. PMID: 10922484.
2- Hollenberg AM, Huber A, Smith CO, Eliseev RA. Electromagnetic stimulation increases mitochondrial function in osteogenic cells and promotes bone fracture repair. Sci Rep. 2021 Sep 27;11(1):19114. Doi: 10.1038/s41598-021-98625-1. PMID: 34580378; PMCID: PMC8476611.
3- Igor V. Semchenko, and Sergei A. Khakhomov. Front. Nanotechnol., 28 April 2023. Sec. Nanomaterials. Volume 5 - 2023 |?https://doi.org/10.3389/fnano.2023.1185429.
4- Sack MN.?The role of SIRT3 in mitochondrial homeostasis and cardiac adaptation to hypertrophy and aging.?J Mol Cell Cardiol.?(2012)?52:520–5. 10.1016/j.yjmcc.2011.11.004?[PMC free article]?[PubMed] [CrossRef]?[Google Scholar.
5- Xie W, Xu R, Fan C, Yang C, Chen H, Cao Y. 900 MHz Radiofrequency Field Induces Mitochondrial Unfolded Protein Response in Mouse Bone Marrow Stem Cells. Front Public Health. 2021 Aug 26; 9:724239. Doi: 10.3389/fpubh.2021.724239. PMID: 34513791; PMCID: PMC8428517
领英推荐
6- Sun L, Zhao L, Peng RY. Research progress in the effects of terahertz waves on biomacromolecules. Mil Med Res. 2021 Apr 25;8(1):28. doi: 10.1186/s40779-021-00321-8. PMID: 33894781; PMCID: PMC8070290.
7- Coutaz, Jean-Louis; Garet, Frederic; Wallace, Vincent P. (2018).?Principles of Terahertz Time-Domain Spectroscopy: An introductory textbook. CRC Press. p.?18.?ISBN?9781351356367?– via Google Books.
8-?Siegel, Peter (2002).?"Studying the Energy of the Universe".?NASA. Education materials. U.S.?National Aeronautics and Space Administration. Retrieved?19 May?2021.
9-?Petrov, Nikolay V.; Maxim S. Kulya; Anton N. Tsypkin; Victor G. Bespalov; Andrei Gorodetsky (5 April 2016).?"Application of Terahertz Pulse Time-Domain Holography for Phase Imaging".?IEEE Transactions on Terahertz Science and Technology.?6?(3): 464–472.?Bibcode:2016ITTST...6..464P.?doi:10.1109/TTHZ.2016.2530938.?S2CID?20563289.
10-?Ahi, Kiarash; Anwar, Mehdi F. (26 May 2016).?"Advanced terahertz techniques for quality control and counterfeit detection". In Anwar, Mehdi F.; Crowe, Thomas W.; Manzur, Tariq (eds.).?Proceedings SPIE Volume 9856, Terahertz Physics, Devices, and Systems X: Advanced Applications in Industry and Defense. SPIE Commercial + Scientific Sensing and Imaging. Baltimore, MD: SPIE: The International Society for Optics and Photonics.?Bibcode:2016SPIE.9856E..0GA.?doi:10.1117/12.2228684.?S2CID?138587594. 98560G. Retrieved?26 May?2016?– via researchgate.net.
11-?Montagnier, L.; Aissa, J.; Giudice, E et al. (8 July 2011). "DNA waves and water".?Journal of Physics: Conference Series 306?(1) :012007 arXiv :1012 .5166 .Bibcode:2011JPhCS.306a2007M.?doi:10.1088/1742.6596/306/1/012007.?S2CID?1810576.
12-?Benveniste, J.; Jurgens, P et al. (1997).?"Transatlantic Transfer of Digitized Antigen Signal by Telephone Link".?Journal of Allergy and Clinical Immunology.?99?(1): S101–S200.?doi:10.1016/S0091-6749(97)81064-0.
13- Meryl K. DNA and cell resonance: magnetic waves enable cell communication. DNA Cell Biol. 2012 Apr;31(4):422-6. Doi: 10.1089/dna.2011.1415. E pub 2011 Oct 19. Retraction in: DNA Cell Biol. 2013 Mar;32(3):138. PMID: 22011216.
14- Ritossa F (1962). "A new puffing pattern induced by temperature shock and DNP in drosophila".?Experimental.?18?(12): 571–573.?doi:10.1007/BF02172188.?ISSN?0014-4754.?S2CID?32525462.
15- Matz JM, Blake MJ, Tatelman HM, Lavoi KP, Holbrook NJ (July 1995). "Characterization and regulation of cold-induced heat shock protein expression in mouse brown adipose tissue".?The American Journal of Physiology.?269?(1 Pt 2): R38–R47.?doi:10.1152/ajpregu.1995.269.1. R38.?PMID?7631901.
16- Cao Y, Ohwatari N, Matsumoto T, Kosaka M, Ohtsuru A, Yamashita S (August 1999). "TGF-beta1 mediates 70-kDa heat shock protein induction due to ultraviolet irradiation in human skin fibroblasts".?Pflügers Archiv.?438?(3): 239–244.?doi:10.1007/s004240050905.?PMID?10398851.?S2CID?28219505.
17- Laplante AF, Moulin V, Auger FA, Landry J, Li H, Morrow G, et?al. (November 1998).?"Expression of heat shock proteins in mouse skin during wound healing".?The Journal of Histochemistry and Cytochemistry.?46?(11): 1291–1301.?doi:10.1177/002215549804601109.?PMID?9774628..
18- De Maio A (January 1999). "Heat shock proteins: facts, thoughts, and dreams".?Shock.?11?(1): 1–12.?Doi:10.1097/00024382-199901000-00001.?PMID?9921710.
19- Wu C (1995). "Heat shock transcription factors: structure and regulation".?Annual Review of Cell and Developmental Biology.?11: 441–469.?doi:10.1146/annurev.cb.11.110195.002301.?PMID?8689565.
20-?Finka A., Goloubinoff P. Proteomic data from human cell cultures refine mechanisms of chaperone mediated protein homeostasis.?Cell Stress Chaperones.?2013; 18:591–605. doi:?10.1007/s12192-013-0413-3.?[PMC free article]?[PubMed] [CrossRef]?[Google Scholar]
21- Sternberg N. Properties of a mutant?Escherichia coli?defective in bacteriophage λ head formation (groE): II. The propagation of phage λ?J. Mol. Biol.?1973; 76:25–44. doi:?10.1016/0022-2836(73)90079-X.?[PubMed] [CrossRef]?[Google Scholar].
22- Gabai VL, Sherman MY. Invited review: Interplay between molecular chaperones and signaling pathways in survival of heat shock. J Appl Physiol. (1985). 2002 Apr;92(4):1743-8. Doi: 10.1152/japplphysiol.01101.2001. PMID: 11896044.
23- Johnson B.D., Schumacher R.J., Ross E.D., Toft D.O. Hop modulates Hsp70/Hsp90 interactions in protein folding.?J. Biol. Chem.?1998; 273:3679–3686. Doi:?10.1074/jbc.273.6.3679.?[PubMed] [CrossRef]?[Google Scholar]
24- Kyratsous C.A., Silverstein S.J., DeLong C.R., Panagiotidis C.A. Chaperone-fusion expression plasmid vectors for improved solubility of recombinant proteins in Escherichia coli.?Gene.?2009; 440:9–15. doi:?10.1016/j.gene.2009.03.011.?[PMC free article]?[PubMed] [CrossRef]?[Google Scholar].
25- Bascos NAD, Landry SJ. A History of Molecular Chaperone Structures in the Protein Data Bank. Int J Mol Sci. 2019 Dec 8;20(24):6195. Doi: 10.3390/ijms20246195. PMID: 31817979; PMCID: PMC6940948
26- Gary Arendash, et al. “A Clinical Trial of Transcranial Electromagnetic Treatment in Alzheimer’s Disease: Cognitive Enhancement and Associated Changes in Cerebrospinal Fluid, Blood, and Brain Imaging”.? Journal of Alzheimer’s Disease?doi:10.3233/JAD-190367.
27- Eleuthera AM, Amici M, Bonfli L, Cesarini V, Ciccolini M, Grimaldi S, Giuliani L, Angeletti M, Fioretti E. 50 Hz extremely low frequency electromagnetic felds enhance protein carbonyl groups content in cancer cells: effects on proteasomal systems. J Biomed Biotechnol. 2009;2009: 834239.
28- Marchesi N, Opera C, Fascine L, et al. Autophagy is modulated in human neuroblastoma cells through direct exposition to low frequency electromagnetic fields. J Cell Physiol. 2014; 229:1776–86.
29- Jeong YJ, Kang GY, Kwon JH, Choi HD, Pack JK, Kim N, Lee YS, Lee HJ. 1950 MHz Electromagnetic Fields Ameliorate Abeta Pathology in Alzheimer’s Disease Mice?Curr. Alzheimer Res. 2015; 12:481–92
30- Perez, F. P., Morisaki, J. J., and Bandeira, J. P. (2019) Repeated Electromagnetic Field Stimulation in Aging and Health, In the Science of Hormesis in Health and Longevity, pp 189–197, Elsevier.
31- 6. Perez FP, Rizkalla J, Jeffers M, et al. The Effect of Repeated Electromagnetic Fields Stimulation in Biological Systems, In The Effect of Electromagnetic Fields on Living Beings. Intech Open;2019.
32- Perez FP, Bandeira JP, et al. Correction to: Multidimensional insights into the repeated electromagnetic field stimulation and biosystems interaction in aging and age-related diseases. J Biomed Sci. 2022 Sep 9;29(1):67. Doi: 10.1186/s12929-022-00836-9. Erratum for: J Biomed Sci. 2022 Jun 13;29(1):39. PMID: 36076241; PMCID: PMC9461117.
33- Kaul G, Thippes wamy H. Role of heat shock proteins in diseases and their therapeutic potential. Indian J Microbiol. 2011 Jun;51(2):124-31. Doi: 10.1007/s12088-011-0147-9. E pub 2011 Feb 9. PMID: 22654152; PMCID: PMC3209880.
34- Tukaj S, Kaminski M. Heat shock proteins in the therapy of autoimmune diseases: too simple to be true? Cell Stress Chaperones. 2019 May;24(3):475-479. Doi: 10.1007/s12192-019-01000-3. E pub 2019 May 9. PMID: 31073900; PMCID: PMC6527538.
35- Kim YS, Alarcon SV, Lee S, et?al.?Update on Hsp90 inhibitors in clinical trial.?Curr Top Med Chem. 2009;9(15):1479‐1492.?[PMC free article]?[PubMed]?[Google Scholar]
36- Hu C, Yang J, Qi Z, Wu H, Wang B, Zou F, Mei H, Liu J, Wang W, Liu Q. Heat shock proteins: Biological functions, pathological roles, and therapeutic opportunities. Med Comm (2020). 2022 Aug 2;3(3): e161. Doi: 10.1002/mco2.161. PMID: 35928554; PMCID: PMC9345296.
37- Torres S., Matías N., Baulies A, et al. Mitochondrial GSH replenishment as a potential therapeutic approach for Niemann Pick type C disease.?Redox Biol.?2017; 11:60–72. doi:?10.1016/j.redox.2016.11.010.?[PMC free article]?[PubMed] [CrossRef]?[Google Scholar].
38- Conde de la Rosa L., Garcia-Ruiz C., Vallejo C, et al. STARD1 promotes NASH-driven HCC by sustaining the generation of bile acids through the alternative mitochondrial pathway.?J. Hepatol.?2021; 74:1429–1441. doi:?10.1016/j.jhep.2021.01.028.?[PMC free article]?[PubMed] [CrossRef]?[Google Scholar].
39- Torres S., Baulies A., Insausti-Urkia N., et al. Endoplasmic reticulum stress-induced upregulation of STARD1 promotes acetaminophen-induced acute liver failure.?Gastroenterology.?2019; 157:552–568. doi:?10.1053/j.gastro.2019.04.023.?[PubMed] [CrossRef]?[Google Scholar]
40- Miller B, Torres M, Jiang X, et al. A Mitochondrial Genome-Wide Association Study of Cataract in a Latino Population. Transl Vis Sci Technol. 2020 May 23;9(6):25. Doi: 10.1167/tvst.9.6.25. PMID: 32821522; PMCID: PMC7408807.
41- Elustondo P, Martin LA, Karten B. Mitochondrial cholesterol import. Biochem.?Biophys Acta Mol Cell Biol Lipids. 2017 Jan;1862(1):90-101. Doi: 10.1016/j.bbalip.2016.08.012. E pub 2016 Aug 23. PMID: 27565112.
42- Astorga J, Gasaly N, Dubois-Camacho K, De la Fuente M, Landskron G, Faber KN, Urra FA, Hermoso MA. The role of cholesterol and mitochondrial bioenergetics in activation of the inflammasome in IBD. Front Immunol. 2022 Nov 18; 13:1028953. Doi: 10.3389/fimmu.2022.1028953. PMID: 36466902; PMCID: PMC9716353.
43- Norat, P., Soldozy, S., Sokolowski, J.D.?et al.?Mitochondrial dysfunction in neurological disorders: Exploring mitochondrial transplantation.?npj Regen Med?5, 22 (2020). https://doi.org/10.1038/s41536-020-00107-x.
44- ?Goicoechea L, Conde de la Rosa L, Torres S, García-Ruiz C, Fernández-Checa JC. Mitochondrial cholesterol: Metabolism and impact on redox biology and disease. Redox Biol. 2023 May; 61:102643. doi: 10.1016/j.redox.2023.102643. Epub 2023 Feb 24. PMID: 36857930; PMCID: PMC9989693
45- Makley LN, McMenimen KA, DeVree BT, et al. Pharmacological chaperone for α-crystallin partially restores transparency in cataract models. i>Science. 2015;350(6261):674-677.
46- Molnar KS, Dunyak BM, Su B, et al. Mechanism of action of VP1-001 in cryAB(R120G)-associated and age-related cataracts. i>Invest Ophthalmol Vis Sci. 2019;60(10):3320-3331.
?