Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Lorenzo Calò
 -- 1860 2023-03-14 11:08:02 |
2 format
Jason Zhu
Meta information modification 1860 2023-03-15 03:13:58 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Bertoldi, G.; Caputo, I.; Driussi, G.; Stefanelli, L.F.; Di Vico, V.; Carraro, G.; Nalesso, F.; Calò, L.A. Altered Pathways in Fabry Disease. Encyclopedia. Available online: https://encyclopedia.pub/entry/42169 (accessed on 27 April 2024).
Bertoldi G, Caputo I, Driussi G, Stefanelli LF, Di Vico V, Carraro G, et al. Altered Pathways in Fabry Disease. Encyclopedia. Available at: https://encyclopedia.pub/entry/42169. Accessed April 27, 2024.
Bertoldi, Giovanni, Ilaria Caputo, Giulia Driussi, Lucia Federica Stefanelli, Valentina Di Vico, Gianni Carraro, Federico Nalesso, Lorenzo A. Calò. "Altered Pathways in Fabry Disease" Encyclopedia, https://encyclopedia.pub/entry/42169 (accessed April 27, 2024).
Bertoldi, G., Caputo, I., Driussi, G., Stefanelli, L.F., Di Vico, V., Carraro, G., Nalesso, F., & Calò, L.A. (2023, March 14). Altered Pathways in Fabry Disease. In Encyclopedia. https://encyclopedia.pub/entry/42169
Bertoldi, Giovanni, et al. "Altered Pathways in Fabry Disease." Encyclopedia. Web. 14 March, 2023.
Altered Pathways in Fabry Disease
Edit
This entry is adapted from the peer-reviewed paper 10.3390/jcm12052063

Fabry disease is a rare X-linked disease characterized by deficient expression and activity of alpha-galactosidase A (α-GalA) with consequent lysosomal accumulation of glycosphingolipid in various organs. Enzyme replacement therapy is the cornerstone of the treatment of all Fabry patients, although in the long-term it fails to completely halt the disease’s progression. This suggests on one hand that the adverse outcomes cannot be justified only by the lysosomal accumulation of glycosphingolipids and on the other that additional therapies targeted at specific secondary mechanisms might contribute to halt the progression of cardiac, cerebrovascular, and renal disease that occur in Fabry patients. 

Fabry disease oxidative stress mitochondria dysfunction impaired autophagy

1. Introduction

The evidence that the available pharmacological treatments fail to completely resolve FD adverse outcomes, mainly at cardiac and renal level, raised the focus on secondary biochemical processes beyond the accumulation of Gb3 and derivatives that might be involved in FD pathogenesis. These may include oxidative stress (OxSt), compromised energy metabolism, impaired autophagy, and disturbed cellular trafficking [1][2][3].

2. Oxidative Stress in Fabry Disease

OxSt occurs when the physiologically generated oxidizing species overwhelm the endogenous antioxidant defenses, resulting in the disruption of the intracellular redox homeostasis [4]. OxSt plays, in fact, a key role in the onset and progression of endothelial dysfunction, atherosclerosis, inflammatory disease, and cardiovascular–renal remodeling [5][6].
In FD, the presence of OxSt was firstly assumed in terms of elevated markers of inflammation and oxidative damage. Shen et al. documented a correlation between Gb3 and increased reactive oxygen species (ROS) production in cultured vascular endothelial cells along with overexpression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin [7]. Moreover, endothelial cells incubated with plasma from FD patients revealed higher ROS generation compared to treatment with plasma from healthy subjects [7].
OxSt also causes damage at nuclear and genomic levels, which results in free radicals damaging DNA and inducing changes in gene expression. Levels of 8-hydroxy-2-dehydroguanosine (8-OHdG), one of the most abundant by-products of DNA oxidation and therefore a non-invasive biomarker of OxSt [8], were found elevated both in the serum [9] and in the myocardial tissue [10] of FD patients with cardiomyopathy, and damage at the DNA level does not seem to be fully restored by endogenous repair mechanisms in FD [11].
The tight association of OxSt with NO dysregulation was also explored in FD. It has been suggested that Gb3 buildup in the endothelium is able to dysregulate the activity of the vasoprotective endothelial nitric oxide synthase (eNOS) while increasing the expression of the inducible NOS (iNOS) [12][13]; iNOS produces larger amounts of NO compared to eNOS, which can easily react with other free radicals, producing reactive nitrogen species (RNS) such as peroxynitrite and spreading the oxidative damage to surrounding macromolecules [14]. In addition, α-GalA knockdown human endothelial cell line showed dramatically enhanced production of 3-Nytrotyrsine (3NT), a marker of nitroxidative damage of proteins, in addition to Gb3 accumulation and reduced eNOS activity [12]. Excesses of 3NT were also found in the dermal and cerebral vessels of FD patients [15] and in the plaque of apolipoprotein-E-deficient mice with α-GalA deficiency and accelerated atherosclerosis [16]. Moreover, tetrahydrobiopterin—an essential cofactor for the normal enzymatic function of NOS—was decreased in the heart and kidney of an animal model of FD and inversely correlated with Gb3 levels in animal tissue and cultured patient cells [17].
Different comparative studies showed activation of OxSt-related pathways in FD compared to healthy subjects. Biancini et al. showed that FD patients exhibit decreased levels of antioxidant defenses, such as glutathione (GSH) and GSH peroxidase (GPX); higher plasma levels of malondialdehyde (MDA), protein carbonyl groups and di-tyrosine in urine together with increased proinflammatory cytokines IL-6 and tumor necrosis factor alpha (TNF-α) [18]. In addition, urinary Gb3 levels were positively correlated with IL-6, carbonyl groups, and MDA plasma levels, suggesting a link between proinflammatory and prooxidant conditions, both likely induced by Gb3 accumulation [18]. This impaired oxidative profile of Fabry patients was further demonstrated, particularly linking the overactive OxSt with the induction of cardiovascular–renal remodeling, which is distinctive of FD [19]. In fact, an overactivation of the mechanism directly involved in ROS production in terms of increased expression of p22phox (subunit of the NADPH oxidase, NOX), a downregulation of heme oxygenase 1 (HO-1), endogenous antioxidant defense, and increased levels of MDA, a marker of lipid peroxidation [19]. It is of note that bilirubin, a potent antioxidant by-product of HO-1 catabolism, was found to be decreased in Fabry patients compared to controls along with reduced total antioxidant status (TAS) [20].
These data further support the hypothesis that OxSt plays an important role in the pathogenesis of the disease with reference to the vascular damage and the cardiovascular-renal remodeling that occur in FD. A better understanding of the specific molecular signaling responses to OxSt in FD could suggest new treatment strategies in order to reduce the high morbidity of these patients.

3. Mithocondrial Dysfunction in Fabry Disease

Mitochondria are known as the cellular energy powerhouse in addition to being an important source of ROS [21]. Mitochondrial ROS (mtROS) are produced as side-products of the oxidative phosphorylation process [22], and a perturbation of the mitochondrial redox homeostasis and the resulting excessive accumulation of mtROS have been linked to the development of several diseases, including cancer, pulmonary and cardiovascular disease, neurodegenerative disorders and diabetes [23].
Mitochondria disfunction has emerged as an harmful factor in the pathophysiology of LSDs, including Gaucher’s disease, Niemann–Pick disease and mucopolysaccharidosis [24]; a dysfunctional mitochondria may in fact impact lysosomal function via generation of ROS as well as depriving the lysosome of ATP, which is required by the V-ATPase proton pump to maintain the acidity of the vacuoles [25]. Insights into a role of mitochondria dysfunction in FD were provided by Lücke and colleagues that documented a reduced activity of mitochondrial respiratory chain (MRC) complexes in skin fibroblasts from FD patients in terms of decreased activity of MRC complex II, IV, and V compared to controls [26]. Impaired oxidative phosphorylation and mitochondrial metabolism as indicated by decreased production of high energy phosphate molecules (e.g., ATP and creatine phosphate) were detected in the hearts of FD subjects [2][27], and downregulation of mitochondrial endonuclease G—critical for cardiac mitochondrial function [28]—was observed in Fabry cardiomyocytes [29]. At the renal level, disturbed mitochondrial structure, metabolism, and turnover were documented in renal tubular epithelial cells from male FD patients [30]. Furthermore, lyso-Gb3 accumulation in podocytes determined the upregulation of the pro-inflammatory and profibrotic Notch1 signaling pathway [31], whose overactivation affects the mitochondrial proteome and impairs mitochondrial metabolism [32]. Additional evidence on the link between OxSt and mitochondrial dysregulation in FD comes from Tseng et al. [33] that reported a downregulation of the protein expression of the superoxide dismutase 2 (SOD2), a mitochondrial antioxidant, in FD-specific human-induced pluripotent stem cells, which was associated with increased ROS generation and enhanced intracellular Gb3 buildup.
Mitochondria are uniquely characterized by their own DNA (mtDNA), a closed-circle double-stranded DNA without histones, which encodes for 37 genes, including 13 components of the mitochondrial electron transport chain [34]. Interestingly, Simoncini et al. investigated whether specific genetic polymorphism in the mitochondrial genome of a cohort of 77 Fabry patients could be accountable for specific FD phenotypes [35]. They showed that certain haploid groups were more prevalent in patients, although there was no observed correlation with gender, age of onset, or organ involvement [35].
The mitochondrial genome is also able to produce specific microRNAs (miRNAs), called mitomiRs, involved in the regulation of mitochondria protein expression and function of mitochondria-related biological processes such as energy metabolism, mitochondrial OxSt, and apoptosis [36]. Recently, a mitomiR dysregulation was unveiled in Fabry patients, shedding light on mitochondria miRNA as critical players in contributing to their aberrant mitochondrial homeostasis and pointing to mitomiRs as a novel class of biomarkers of FD [37].

4. Impaired Autophagy in Fabry Disease

Lysosomes are critically involved in the maintenance of cellular homeostasis, driving the degradation and recycling of metabolic wastes, dysfunctional organelles such as mitochondria (i.e., mitophagy [38]), or large cytosolic molecules, especially in response to environmental stress. This process takes place via the autophagy–lysosome pathway (ALP), a process that seizes cytoplasmic cargos into double-membraned vesicles called autophagosomes and direct them toward lysosomes [39]. Since autophagy plays a key role in the clearance of lysosomal substrates [40], increasing evidence suggests a key role of autophagic (dys)function in FD pathophysiology. In fact, several studies reported an autophagic dysregulation in different models of FD. Chévrier et al. firstly documented an upregulation of the autophagic marker microtubule-associated protein light-chain 3 (LC3-II) in human Fabry skin fibroblasts and in kidney biopsies along with accumulation of autophagic vacuoles in FD renal cells, assuming a disturbance of the autophagic pathway [41]. Alteration of autophagic pathways was further confirmed in α-GalA deficient podocytes that, in addition to marked upregulation of LC3-II levels, showed a decreased activity of the mammalian target of rapamycin (mTOR) kinase, a negative regulator of autophagic vesicle formation, suggesting that the overactive autophagy, beyond Gb3 accumulation, may be an additional contributor to podocyte damage and glomerular injury occurring in Fabry patients [42]. Moreover, autophagy was recently addressed as a key mechanism triggering renal tubulointerstitial fibrosis in an animal model of FD [43]. The role of autophagy disorders in FD was also assessed in the context of neurological [44] and corneal [45] complications.
In LSDs, the lysosomal trapping of sphingolipids within lysosomes and the altered lipid recycling and trafficking has a direct effect on the lipid composition and the biophysical properties of plasma and intracellular membranes [2][46]. In FD, changes in the lipid composition of membranes were assessed in patients’ fibroblasts [47], in the inner mitochondrial membrane [48], and in specialized intracellular membrane domains termed lipid rafts [49]. Consequently, changes in the lipid composition may alter the stoichiometry and functionality of their protein components (e.g., ion channels [50][51]), further perturbing the signal transduction.
This disturbed intracellular environment might also affect ERT efficacy since the therapeutic effect relays on the proper intracellular uptake of the infused enzyme via the endolysosomal pathway. After the binding of the administered enzyme with a membrane receptor—such mannose-6-phosphate receptor (M6PR), megalin, or sortilin [52]—an essential component in the trafficking is the generation and maintenance of a proper low endolysosomal pH gradient, which enables dissociation between the receptors and their ligands, the recycling of receptors back to the apical membrane, and the progression of the vesicles toward lysosomes [53]. A key protein involved in the vesicular acidification is the chloride channel Cl−/H+ antiporter ClC-5, mainly located in the early endosomes [53]. In this regard, in renal proximal tubule cells, a loss of ClC-5 was associated with trafficking defect along with lysosomal dysfunction, OxSt, and dedifferentiation [54]. Moreover, a downregulation of ClC-5—along with cubilin and megalin, two endocytic receptors responsible for the reabsorption of the vast majority of proteins filtered in the glomeruli—was cytologically assessed in renal biopsies of two cases of FD [55]. Therefore, it is reasonable that ClC-5 downregulation and the following impaired intracellular trafficking might affect and limit the therapeutic effect of ERT towards the natural progression of the disease.
Finally, the above-described endosomal–lysosomal abnormalities have been recently associated with the likely protection from COVID-19 that Fabry patients seem to exhibit, in view of the unfavorable host cellular environment for SARS-CoV-2 infection and propagation, that does not seem to be affected by ERT treatment [56]. However, a molecular mechanistic explanation of this naturally occurring protection is still unknown.

References

  1. Ravarotto, V.; Simioni, F.; Carraro, G.; Bertoldi, G.; Pagnin, E.; Calò, L.A. Oxidative Stress and Cardiovascular-Renal Damage in Fabry Disease: Is There Room for a Pathophysiological Involvement? J. Clin. Med. 2018, 7, 409.
  2. Das, A.M.; Naim, H.Y. Biochemical Basis of Fabry Disease with Emphasis on Mitochondrial Function and Protein Trafficking. Adv. Clin. Chem. 2009, 49, 57–71.
  3. Ivanova, M. Altered Sphingolipids Metabolism Damaged Mitochondrial Functions: Lessons Learned from Gaucher and Fabry Diseases. J. Clin. Med. 2020, 9, 1116.
  4. Sies, H. Oxidative Stress; Academic Press: London, UK, 1985; ISBN 978-0-12-642760-8.
  5. Ravarotto, V.; Bertoldi, G.; Innico, G.; Gobbi, L.; Calò, L.A. The Pivotal Role of Oxidative Stress in the Pathophysiology of Cardiovascular-Renal Remodeling in Kidney Disease. Antioxidants 2021, 10, 1041.
  6. Ravarotto, V.; Bertoldi, G.; Stefanelli, L.F.; Nalesso, F.; Calò, L.A. Pathomechanism of Oxidative Stress in Cardiovascularrenal Remodeling and Therapeutic Strategies. Kidney Res. Clin. Pract. 2022, 41, 533–544.
  7. Shen, J.S.; Meng, X.L.; Moore, D.F.; Quirk, J.M.; Shayman, J.A.; Schiffmann, R.; Kaneski, C.R. Globotriaosylceramide Induces Oxidative Stress and Up-Regulates Cell Adhesion Molecule Expression in Fabry Disease Endothelial Cells. Mol. Genet. Metab. 2008, 95, 163–168.
  8. Chiou, C.C.; Chang, P.Y.; Chan, E.C.; Wu, T.L.; Tsao, K.C.; Wu, J.T. Urinary 8-Hydroxydeoxyguanosine and Its Analogs as DNA Marker of Oxidative Stress: Development of an ELISA and Measurement in Both Bladder and Prostate Cancers. Clin. Chim. Acta 2003, 334, 87–94.
  9. Chen, K.H.; Chou, Y.C.; Hsiao, C.Y.; Chien, Y.; Wang, K.L.; Lai, Y.H.; Chang, Y.L.; Niu, D.M.; Yu, W.C. Amelioration of Serum 8-OHdG Level by Enzyme Replacement Therapy in Patients with Fabry Cardiomyopathy. Biochem. Biophys. Res. Commun. 2017, 486, 293–299.
  10. Chimenti, C.; Scopelliti, F.; Vulpis, E.; Tafani, M.; Villanova, L.; Verardo, R.; De Paulis, R.; Russo, M.A.; Frustaci, A. Increased Oxidative Stress Contributes to Cardiomyocyte Dysfunction and Death in Patients with Fabry Disease Cardiomyopathy. Hum. Pathol. 2015, 46, 1760–1768.
  11. Biancini, G.B.; Moura, D.J.; Manini, P.R.; Faverzani, J.L.; Netto, C.B.O.; Deon, M.; Giugliani, R.; Saffi, J.; Vargas, C.R. DNA Damage in Fabry Patients: An Investigation of Oxidative Damage and Repair. Mutat. Research. Genet. Toxicol. Environ. Mutagen. 2015, 784–785, 31–36.
  12. Shu, L.; Vivekanandan-Giri, A.; Pennathur, S.; Smid, B.E.; Aerts, J.M.F.G.; Hollak, C.E.M.; Shayman, J.A. Establishing 3-Nitrotyrosine as a Biomarker for the Vasculopathy of Fabry Disease. Kidney Int. 2014, 86, 58–66.
  13. Namdar, M.; Gebhard, C.; Studiger, R.; Shi, Y.; Mocharla, P.; Schmied, C.; Brugada, P.; Lüscher, T.F.; Camici, G.G. Globotriaosylsphingosine Accumulation and Not Alpha-Galactosidase-A Deficiency Causes Endothelial Dysfunction in Fabry Disease. PloS ONE 2012, 7, e36373.
  14. Sun, J.; Druhan, L.J.; Zweier, J.L. Reactive Oxygen and Nitrogen Species Regulate Inducible Nitric Oxide Synthase Function Shifting the Balance of Nitric Oxide and Superoxide Production. Arch. Biochem. Biophys. 2010, 494, 130–137.
  15. Moore, D.F.; Scott, L.T.C.; Gladwin, M.T.; Altarescu, G.; Kaneski, C.; Suzuki, K.; Pease-Fye, M.; Ferri, R.; Brady, R.O.; Herscovitch, P.; et al. Regional Cerebral Hyperperfusion and Nitric Oxide Pathway Dysregulation in Fabry Disease: Reversal by Enzyme Replacement Therapy. Circulation 2001, 104, 1506–1512.
  16. Bodary, P.F.; Shen, Y.; Vargas, F.B.; Bi, X.; Ostenso, K.A.; Gu, S.; Shayman, J.A.; Eitzman, D.T. α-Galactosidase A Deficiency Accelerates Atherosclerosis in Mice with Apolipoprotein E Deficiency. Circulation 2005, 111, 629–632.
  17. Shen, J.S.; Arning, E.; West, M.L.; Day, T.S.; Chen, S.; Meng, X.L.; Forni, S.; McNeill, N.; Goker-Alpan, O.; Wang, X.; et al. Tetrahydrobiopterin Deficiency in the Pathogenesis of Fabry Disease. Hum. Mol. Genet. 2017, 26, 1182–1192.
  18. Biancini, G.B.; Vanzin, C.S.; Rodrigues, D.B.; Deon, M.; Ribas, G.S.; Barschak, A.G.; Manfredini, V.; Netto, C.B.O.; Jardim, L.B.; Giugliani, R.; et al. Globotriaosylceramide Is Correlated with Oxidative Stress and Inflammation in Fabry Patients Treated with Enzyme Replacement Therapy. Biochim. Biophys. Acta 2012, 1822, 226–232.
  19. Ravarotto, V.; Carraro, G.; Pagnin, E.; Bertoldi, G.; Simioni, F.; Maiolino, G.; Martinato, M.; Landini, L.; Davis, P.A.; Calò, L.A. Oxidative Stress and the Altered Reaction to It in Fabry Disease: A Possible Target for Cardiovascular-Renal Remodeling? PLoS ONE 2018, 13, e0204618.
  20. Jirásková, A.; Bortolussi, G.; Dostálová, G.; Eremiášová, L.; Golaň, L.; Danzig, V.; Linhart, A.; Vítek, L. Serum Bilirubin Levels and Promoter Variations in HMOX1 and UGT1A1 Genes in Patients with Fabry Disease. Oxid. Med. Cell. Longev. 2017, 2017.
  21. Turrens, J.F. Mitochondrial Formation of Reactive Oxygen Species. J. Physiol. 2003, 552, 335–344.
  22. Nohl, H.; Gille, L.; Staniek, K. Intracellular Generation of Reactive Oxygen Species by Mitochondria. Biochem. Pharmacol. 2005, 69, 719–723.
  23. Patergnani, S.; Bouhamida, E.; Leo, S.; Pinton, P.; Rimessi, A. Mitochondrial Oxidative Stress and “Mito-Inflammation”: Actors in the Diseases. Biomedicines 2021, 9, 216.
  24. Plotegher, N.; Duchen, M.R. Mitochondrial Dysfunction and Neurodegeneration in Lysosomal Storage Disorders. Trends Mol. Med. 2017, 23, 116–134.
  25. Stepien, K.M.; Roncaroli, F.; Turton, N.; Hendriksz, C.J.; Roberts, M.; Heaton, R.A.; Hargreaves, I. Mechanisms of Mitochondrial Dysfunction in Lysosomal Storage Disorders: A Review. J. Clin. Med. 2020, 9, 2596.
  26. Lücke, T.; Höppner, W.; Schmidt, E.; Illsinger, S.; Das, A.M. Fabry Disease: Reduced Activities of Respiratory Chain Enzymes with Decreased Levels of Energy-Rich Phosphates in Fibroblasts. Mol. Genet. Metab. 2004, 82, 93–97.
  27. Machann, W.; Breunig, F.; Weidemann, F.; Sandstede, J.; Hahn, D.; Köstler, H.; Neubauer, S.; Wanner, C.; Beer, M. Cardiac Energy Metabolism Is Disturbed in Fabry Disease and Improves with Enzyme Replacement Therapy Using Recombinant Human Galactosidase, A. Eur. J. Heart Fail. 2011, 13, 278–283.
  28. McDermott-Roe, C.; Ye, J.; Ahmed, R.; Sun, X.-M.; Serafín, A.; Ware, J.; Bottolo, L.; Muckett, P.; Cañas, X.; Zhang, J.; et al. Endonuclease G Is a Novel Determinant of Cardiac Hypertrophy and Mitochondrial Function. Nature 2011, 478, 114–118.
  29. Birket, M.J.; Raibaud, S.; Lettieri, M.; Adamson, A.D.; Letang, V.; Cervello, P.; Redon, N.; Ret, G.; Viale, S.; Wang, B.; et al. A Human Stem Cell Model of Fabry Disease Implicates LIMP-2 Accumulation in Cardiomyocyte Pathology. Stem Cell Rep. 2019, 13, 380–393.
  30. Schumann, A.; Schaller, K.; Belche, V.; Cybulla, M.; Grünert, S.C.; Moers, N.; Sass, J.O.; Kaech, A.; Hannibal, L.; Spiekerkoetter, U. Defective Lysosomal Storage in Fabry Disease Modifies Mitochondrial Structure, Metabolism and Turnover in Renal Epithelial Cells. J. Inherit. Metab. Dis. 2021, 44, 1039–1050.
  31. Sanchez-Niño, M.D.; Carpio, D.; Sanz, A.B.; Ruiz-Ortega, M.; Mezzano, S.; Ortiz, A. Lyso-Gb3 Activates Notch1 in Human Podocytes. Hum. Mol. Genet. 2015, 24, 5720–5732.
  32. Basak, N.P.; Roy, A.; Banerjee, S. Alteration of Mitochondrial Proteome Due to Activation of Notch1 Signaling Pathway. J. Biol. Chem. 2014, 289, 7320–7334.
  33. Tseng, W.-L.; Chou, S.-J.; Chiang, H.-C.; Wang, M.-L.; Chien, C.-S.; Chen, K.-H.; Leu, H.-B.; Wang, C.-Y.; Chang, Y.-L.; Liu, Y.-Y.; et al. Imbalanced Production of Reactive Oxygen Species and Mitochondrial Antioxidant SOD2 in Fabry Disease-Specific Human Induced Pluripotent Stem Cell-Differentiated Vascular Endothelial Cells. Cell Transpl. 2017, 26, 513–527.
  34. Taylor, R.W.; Turnbull, D.M. Mitochondrial DNA Mutations in Human Disease. Nat. Rev. Genet. 2005, 6, 389–402.
  35. Simoncini, C.; Chico, L.; Concolino, D.; Sestito, S.; Fancellu, L.; Boadu, W.; Sechi, G.P.; Feliciani, C.; Gnarra, M.; Zampetti, A.; et al. Mitochondrial DNA Haplogroups May Influence Fabry Disease Phenotype. Neurosci. Lett. 2016, 629, 58–61.
  36. Song, R.; Hu, X.-Q.; Zhang, L. Mitochondrial MiRNA in Cardiovascular Function and Disease. Cells 2019, 8, 1475.
  37. Gambardella, J.; Fiordelisi, A.; Sorriento, D.; Cerasuolo, F.; Buonaiuto, A.; Avvisato, R.; Pisani, A.; Varzideh, F.; Riccio, E.; Santulli, G.; et al. Mitochondrial MicroRNAs Are Dysregulated in Patients with Fabry Disease. J. Pharm. Exp. Ther. 2023, 384, 72–78.
  38. King, L.; Plun-Favreau, H. Chapter 5—Mitophagy. In Parkinson’s Disease; Verstreken, P., Ed.; Academic Press: San Diego, CA, USA, 2017; pp. 139–177. ISBN 978-0-12-803783-6.
  39. Lavandero, S.; Chiong, M.; Rothermel, B.A.; Hill, J.A. Autophagy in Cardiovascular Biology. J. Clin. Investig. 2015, 125, 55–64.
  40. Festa, B.P.; Chen, Z.; Berquez, M.; Debaix, H.; Tokonami, N.; Prange, J.A.; van de Hoek, G.; Alessio, C.; Raimondi, A.; Nevo, N.; et al. Impaired Autophagy Bridges Lysosomal Storage Disease and Epithelial Dysfunction in the Kidney. Nat. Commun. 2018, 9, 161.
  41. Chévrier, M.; Brakch, N.; Céline, L.; Genty, D.; Ramdani, Y.; Moll, S.; Djavaheri-Mergny, M.; Brasse-Lagnel, C.; Annie Laquerrière, A.L.; Barbey, F.; et al. Autophagosome Maturation Is Impaired in Fabry Disease. Autophagy 2010, 6, 589–599.
  42. Liebau, M.C.; Braun, F.; Höpker, K.; Weitbrecht, C.; Bartels, V.; Müller, R.-U.; Brodesser, S.; Saleem, M.A.; Benzing, T.; Schermer, B.; et al. Dysregulated Autophagy Contributes to Podocyte Damage in Fabry’s Disease. PLoS ONE 2013, 8, e63506.
  43. Chung, S.; Son, M.; Chae, Y.; Oh, S.; Koh, E.S.; Kim, Y.K.; Shin, S.J.; Park, C.W.; Jung, S.-C.; Kim, H.-S. Fabry Disease Exacerbates Renal Interstitial Fibrosis after Unilateral Ureteral Obstruction via Impaired Autophagy and Enhanced Apoptosis. Kidney Res. Clin. Pr. 2021, 40, 208–219.
  44. Nelson, M.P.; Tse, T.E.; O’Quinn, D.B.; Percival, S.M.; Jaimes, E.A.; Warnock, D.G.; Shacka, J.J. Autophagy-Lysosome Pathway Associated Neuropathology and Axonal Degeneration in the Brains of Alpha-Galactosidase A-Deficient Mice. Acta Neuropathol. Commun. 2014, 2, 20.
  45. Marenco, M.; Segatto, M.; Sacchetti, M.; Mangiantini, P.; Giovannetti, F.; Plateroti, R. Autophagy-Lysosome Pathway Alteration in Ocular Surface Manifestations in Fabry Disease Patients. Orphanet J. Rare Dis. 2022, 17, 291.
  46. Platt, F.M.; Boland, B.; van der Spoel, A.C. The Cell Biology of Disease: Lysosomal Storage Disorders: The Cellular Impact of Lysosomal Dysfunction. J. Cell Biol. 2012, 199, 723–734.
  47. Maalouf, K.; Jia, J.; Rizk, S.; Brogden, G.; Keiser, M.; Das, A.; Naim, H.Y. A Modified Lipid Composition in Fabry Disease Leads to an Intracellular Block of the Detergent-Resistant Membrane-Associated Dipeptidyl Peptidase IV. J. Inherit. Metab. Dis. 2010, 33, 445–449.
  48. Song, H.-Y.; Chien, C.-S.; Yarmishyn, A.A.; Chou, S.-J.; Yang, Y.-P.; Wang, M.-L.; Wang, C.-Y.; Leu, H.-B.; Yu, W.-C.; Chang, Y.-L.; et al. Generation of GLA-Knockout Human Embryonic Stem Cell Lines to Model Autophagic Dysfunction and Exosome Secretion in Fabry Disease-Associated Hypertrophic Cardiomyopathy. Cells 2019, 8, 327.
  49. Labilloy, A.; Youker, R.T.; Bruns, J.R.; Kukic, I.; Kiselyov, K.; Halfter, W.; Finegold, D.; do Monte, S.J.H.; Weisz, O.A. Altered Dynamics of a Lipid Raft Associated Protein in a Kidney Model of Fabry Disease. Mol. Genet. Metab. 2014, 111, 184–192.
  50. Weissmann, C.; Albanese, A.A.; Contreras, N.E.; Gobetto, M.N.; Castellanos, L.C.S.; Uchitel, O.D. Ion Channels and Pain in Fabry Disease. Mol. Pain 2021, 17, 17448069211033172.
  51. Tuttolomondo, A.; Simonetta, I.; Riolo, R.; Todaro, F.; Di Chiara, T.; Miceli, S.; Pinto, A. Pathogenesis and Molecular Mechanisms of Anderson–Fabry Disease and Possible New Molecular Addressed Therapeutic Strategies. Int. J. Mol. Sci. 2021, 22, 10088.
  52. Prabakaran, T.; Nielsen, R.; Larsen, J.V.; Sørensen, S.S.; Rasmussen, U.F.-; Saleem, M.A.; Petersen, C.M.; Verroust, P.J.; Christensen, E.I. Receptor-Mediated Endocytosis of α-Galactosidase A in Human Podocytes in Fabry Disease. PLoS ONE 2011, 6, e25065.
  53. Rega, L.R.; De Leo, E.; Nieri, D.; Luciani, A. Defective Cystinosin, Aberrant Autophagy−Endolysosome Pathways, and Storage Disease: Towards Assembling the Puzzle. Cells 2022, 11, 326.
  54. Devuyst, O.; Luciani, A. Chloride Transporters and Receptor-Mediated Endocytosis in the Renal Proximal Tubule. J Physiol 2015, 593, 4151–4164.
  55. Trimarchi, H.; Ceol, M.; Gianesello, L.; Priante, G.; Iotti, A.; Del Prete, D. Downregulation of Megalin, Cubilin, ClC-5 and Podocin in Fabry Nephropathy: Potential Implications in the Decreased Effectiveness of Enzyme Replacement Therapy. J. Nephrol. 2021, 34, 1307–1314.
  56. Pieroni, M.; Pieruzzi, F.; Mignani, R.; Graziani, F.; Olivotto, I.; Riccio, E.; Ciabatti, M.; Limongelli, G.; Manna, R.; Bolognese, L.; et al. Potential Resistance to SARS-CoV-2 Infection in Lysosomal Storage Disorders. Clin. Kidney J. 2021, 14, 1488–1490.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Urology & Nephrology; Medicine, General & Internal; Biochemistry & Molecular Biology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Giovanni Bertoldi
,
Ilaria Caputo
,
Giulia Driussi
,
Lucia Federica Stefanelli
,
Valentina Di Vico
,
Gianni Carraro
,
Federico Nalesso
,
Lorenzo A. Calò
View Times: 237
Revisions: 2 times (View History)
Update Date: 15 Mar 2023
Table of Contents
    1000/1000
    Hot Most Recent
    Feedback