Genistein Activates Transcription Factor EB and Corrects Niemann–Pick C Phenotype
Abstract
:1. Introduction
2. Results
2.1. Genistein Promotes TFEB Nuclear Translocation in NPC Pharmacological and Genetic Models
2.2. Genistein Induces TFEB Target Gene Transcription in NPC1 Patient Fibroblasts
2.3. Genistein Induces Autophagy in NPC1 Patient Fibroblasts
2.4. Genistein Induces Lysosomal Exocytosis and Alleviates Cholesterol Accumulation in NPC Cells
3. Discussion
4. Material and Methods
4.1. Cell Culture
4.2. Genistein and U18666A Treatments
4.3. Reagents and Antibodies
4.4. Nuclei-Cytoplasmic Fractions
4.5. High Content Nuclear Translocation Assay
4.6. Immunoblot Analysis
4.7. RNA Isolation
4.8. cDNA Synthesis and Quantitative Polymerase Chain Reaction (qPCR)
4.9. Measurement β-Hexosaminidase Release
4.10. Filipin Staining
5. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Winkler, M.B.; Kidmose, R.T.; Szomek, M.; Thaysen, K.; Rawson, S.; Muench, S.P.; Wüstner, D.; Pedersen, B.P. Structural Insight into Eukaryotic Sterol Transport through Niemann-Pick Type C Proteins. Cell 2019, 179, 485–497.e18. [Google Scholar] [CrossRef]
- Liao, G.; Yao, Y.; Liu, J.; Yu, Z.; Cheung, S.; Xie, A.; Liang, X.; Bi, X. Cholesterol accumulation is associated with lysosomal dysfunction and autophagic stress in NPC1 -/- mouse brain. Am. J. Pathol. 2007, 171, 962–975. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vázquez, M.C.; Balboa, E.; Alvarez, A.R.; Zanlungo, S. Oxidative Stress: A Pathogenic Mechanism for Niemann-Pick Type C Disease. Oxidative Med. Cell. Longev. 2012, 2012, 205713. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Meske, V.; Erz, J.; Priesnitz, T.; Ohm, T.-G. The autophagic defect in Niemann–Pick disease type C neurons differs from somatic cells and reduces neuronal viability. Neurobiol. Dis. 2014, 64, 88–97. [Google Scholar] [CrossRef] [PubMed]
- Torres, S.; Balboa, E.; Zanlungo, S.; Enrich, C.; Garcia-Ruiz, C.; Fernandez-Checa, J.C. Lysosomal and Mitochondrial Liaisons in Niemann-Pick Disease. Front. Physiol. 2017, 8, 982. [Google Scholar] [CrossRef] [Green Version]
- Beltroy, E.P.; Richardson, J.A.; Horton, J.D.; Turley, S.D.; Dietschy, J.M. Cholesterol accumulation and liver cell death in mice with Niemann-Pick type C disease. Hepatology 2005, 42, 886–893. [Google Scholar] [CrossRef]
- Pentchev, P.G. Niemann–Pick C research from mouse to gene. Biochim. Biophys. Acta (BBA)—Mol. Cell Biol. Lipids 2004, 1685, 3–7. [Google Scholar] [CrossRef] [PubMed]
- Geberhiwot, T.; on behalf of the International Niemann-Pick Disease Registry (INPDR); Moro, A.; Dardis, A.; Ramaswami, U.; Sirrs, S.; Marfa, M.P.; Vanier, M.T.; Walterfang, M.; Bolton, S.; et al. Consensus clinical management guidelines for Niemann-Pick disease type C. Orphanet J. Rare Dis. 2018, 13, 1–19. [Google Scholar] [CrossRef] [Green Version]
- Ballabio, A.; Bonifacino, J.S. Lysosomes as dynamic regulators of cell and organismal homeostasis. Nat. Rev. Mol. Cell Biol. 2020, 21, 101–118. [Google Scholar] [CrossRef]
- Lieberman, A.P.; Puertollano, R.; Raben, N.; Slaugenhaupt, S.; Walkley, S.U.; Ballabio, A. Autophagy in lysosomal storage disorders. Autophagy 2012, 8, 719–730. [Google Scholar] [CrossRef] [Green Version]
- Pacheco, C.D.; Lieberman, A.P. Lipid Trafficking Defects Increase Beclin-1 and Activate Autophagy in Niemann-Pick Type C Disease. Autophagy 2007, 3, 487–489. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pacheco, C.D.; Lieberman, A.P. The pathogenesis of Niemann–Pick type C disease: A role for autophagy? Expert Rev. Mol. Med. 2008, 10, e26. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ishibashi, S.; Yamazaki, T.; Okamoto, K. Association of autophagy with cholesterol-accumulated compartments in Nie-mann-Pick disease type C cells. J. Clin. Neurosci. 2009, 16, 954–959. [Google Scholar] [CrossRef] [PubMed]
- Elrick, M.J.; Yu, T.; Chung, C.; Lieberman, A.P. Impaired proteolysis underlies autophagic dysfunction in Niemann–Pick type C disease. Hum. Mol. Genet. 2012, 21, 4876–4887. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sobo, K.; Le Blanc, I.; Luyet, P.-P.; Fivaz, M.; Ferguson, C.; Parton, R.G.; Gruenberg, J.; Van Der Goot, F.G. Late Endosomal Cholesterol Accumulation Leads to Impaired Intra-Endosomal Trafficking. PLoS ONE 2007, 2, e851. [Google Scholar] [CrossRef]
- Fraldi, A.; Annunziata, F.; Lombardi, A.; Kaiser, H.-J.; Medina, D.L.; Spampanato, C.; Fedele, A.O.; Polishchuk, R.; Sorrentino, N.C.; Simons, K.; et al. Lysosomal fusion and SNARE function are impaired by cholesterol accumulation in lysosomal storage disorders. EMBO J. 2010, 29, 3607–3620. [Google Scholar] [CrossRef] [Green Version]
- Koga, H.; Kaushik, S.; Cuervo, A.M. Altered lipid content inhibits autophagic vesicular fusion. FASEB J. 2010, 24, 3052–3065. [Google Scholar] [CrossRef] [Green Version]
- Sarkar, S.; Carroll, B.; Buganim, Y.; Maetzel, D.; Ng, A.H.; Cassady, J.P.; Cohen, M.A.; Chakraborty, S.; Wang, H.; Spooner, E.; et al. Impaired Autophagy in the Lipid-Storage Disorder Niemann-Pick Type C1 Disease. Cell Rep. 2013, 5, 1302–1315. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hetmańczyk-Sawicka, K.; Iwanicka-Nowicka, R.; Fogtman, A.; Cieśla, J.; Włodarski, P.; Żyżyńska-Granica, B.; Filocamo, M.; Dardis, A.; Peruzzo, P.; Bednarska-Makaruk, M.; et al. Changes in global gene expression indicate disordered autophagy, apoptosis and inflammatory processes and downregulation of cytoskeletal signalling and neuronal development in patients with Niemann-Pick C disease. Neurogenetics 2020, 21, 105–119. [Google Scholar] [CrossRef]
- Choi, A.M.; Ryter, S.W.; Levine, B. Autophagy in Human Health and Disease. N. Engl. J. Med. 2013, 368, 651–662. [Google Scholar] [CrossRef]
- Sardiello, M.; Palmieri, M.; Di Ronza, A.; Medina, D.L.; Valenza, M.; Gennarino, V.A.; Di Malta, C.; Donaudy, F.; Embrione, V.; Polishchuk, R.S.; et al. A Gene Network Regulating Lysosomal Biogenesis and Function. Science 2009, 325, 473–477. [Google Scholar] [CrossRef] [Green Version]
- Palmieri, M.; Impey, S.; Kang, H.; Di Ronza, A.; Pelz, C.; Sardiello, M.; Ballabio, A. Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways. Hum. Mol. Genet. 2011, 20, 3852–3866. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sardiello, M.; Ballabio, A. Lysosomal enhancement: A CLEAR answer to cellular degradative needs. Cell Cycle 2009, 8, 4021–4022. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Medina, D.L.; Fraldi, A.; Bouche, V.; Annunziata, F.; Mansueto, G.; Spampanato, C.; Puri, C.; Pignata, A.; Martina, J.A.; Sardiello, M.; et al. Transcriptional activation of lysosomal exocytosis pro-motes cellular clearance. Dev. Cell 2011, 21, 421–430. [Google Scholar] [CrossRef] [PubMed]
- Sardiello, M. Transcription factor EB: From master coordinator of lysosomal pathways to candidate therapeutic target in degenerative storage diseases. Ann. N. Y. Acad. Sci. 2016, 1371, 3–14. [Google Scholar] [CrossRef] [PubMed]
- Settembre, C.; Ballabio, A. TFEB regulates autophagy: An integrated coordination of cellular degradation and recycling pro-cesses. Autophagy 2011, 7, 1379–1381. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Settembre, C.; De Cegli, R.; Mansueto, G.; Saha, P.K.; Vetrini, F.; Visvikis, O.; Huynh, T.; Carissimo, A.; Palmer, D.; Klisch, T.J.; et al. TFEB controls cellular lipid metabolism through a star-vation-induced autoregulatory loop. Nat. Cell Biol. 2013, 15, 647–658. [Google Scholar]
- Buratta, S.; Tancini, B.; Sagini, K.; Delo, F.; Chiaradia, E.; Urbanelli, L.; Emiliani, C. Lysosomal Exocytosis, Exosome Release and Secretory Autophagy: The Autophagic- and Endo-Lysosomal Systems Go Extracellular. Int. J. Mol. Sci. 2020, 21, 2576. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xu, Y.; Du, S.; Marsh, J.A.; Horie, K.; Sato, C.; Ballabio, A.; Karch, C.M.; Holtzman, D.M.; Zheng, H. TFEB regulates lysosomal exocytosis of tau and its loss of function exacerbates tau pathology and spreading. Mol. Psychiatry 2020, 1–15. [Google Scholar] [CrossRef]
- Samie, M.A.; Xu, H. Lysosomal exocytosis and lipid storage disorders. J. Lipid Res. 2014, 55, 995–1009. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Marques, A.R.A.; Saftig, P. Lysosomal storage disorders—Challenges, concepts and avenues for therapy: Beyond rare diseases. J. Cell Sci. 2019, 132, jcs221739. [Google Scholar] [CrossRef]
- Tsunemi, T.; Perez-Rosello, T.; Ishiguro, Y.; Yoroisaka, A.; Jeon, S.; Hamada, K.; Rammonhan, M.; Wong, Y.C.; Xie, Z.; Akamatsu, W.; et al. Increased Lysosomal Exocytosis Induced by Lysosomal Ca2+ Channel Agonists Protects Human Dopaminergic Neurons from α-Synuclein Toxicity. J. Neurosci. 2019, 39, 5760–5772. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Spampanato, C.; Feeney, E.; Li, L.; Cardone, M.; Lim, J.-A.; Annunziata, F.; Zare, H.; Polishchuk, R.; Puertollano, R.; Parenti, G.; et al. Transcription factor EB (TFEB) is a new therapeutic target for Pompe disease. EMBO Mol. Med. 2013, 5, 691–706. [Google Scholar] [CrossRef] [PubMed]
- Feeney, E.J.; Spampanato, C.; Puertollano, R.; Ballabio, A.; Parenti, G.; Raben, N. What else is in store for autophagy? Ex-ocytosis of autolysosomes as a mechanism of TFEB-mediated cellular clearance in Pompe disease. Autophagy 2013, 9, 1117–1118. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pastore, N.; Blomenkamp, K.; Annunziata, F.; Piccolo, P.; Mithbaokar, P.; Sepe, R.M.; Vetrini, F.; Palmer, D.; Ng, P.; Polishchuk, E.; et al. Gene transfer of master autophagy regulator TFEB results in clearance of toxic protein and correction of hepatic disease in alpha-1-anti-trypsin deficiency. EMBO Mol. Med. 2013, 5, 397–412. [Google Scholar] [CrossRef]
- Ballabio, A. The awesome lysosome. EMBO Mol. Med. 2016, 8, 73–76. [Google Scholar] [CrossRef]
- A Polito, V.; Li, H.; Martini-Stoica, H.; Wang, B.; Yang, L.; Xu, Y.; Swartzlander, D.B.; Palmieri, M.; Di Ronza, A.; Lee, V.M.; et al. Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB. EMBO Mol. Med. 2014, 6, 1142–1160. [Google Scholar] [CrossRef]
- Xiao, Q.; Yan, P.; Ma, X.; Liu, H.; Perez, R.; Zhu, A.; Gonzales, E.R.; Tripoli, D.L.; Czerniewski, L.; Ballabio, A.; et al. Neuronal-Targeted TFEB Accelerates Lysosomal Degradation of APP, Reducing A Generation and Amyloid Plaque Pathogenesis. J. Neurosci. 2015, 35, 12137–12151. [Google Scholar] [CrossRef] [Green Version]
- Palmieri, M.; Pal, R.; Nelvagal, H.R.; Lotfi, P.; Stinnett, G.R.; Seymour, M.L.; Chaudhury, A.; Bajaj, L.; Bondar, V.V.; Bremner, L.; et al. Corrigendum: mTORC1-independent TFEB activation via Akt inhibition promotes cellular clearance in neuro-degenerative storage diseases. Nat. Commun. 2017, 8, 15793. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tsunemi, T.; Ashe, T.D.; Morrison, B.E.; Soriano, K.R.; Au, J.; Roque, R.A.; Lazarowski, E.R.; Damian, V.A.; Masliah, E.; La Spada, A.R. PGC-1α rescues Huntington’s disease proteotoxicity by preventing oxidative stress and promoting TFEB function. Sci. Transl. Med. 2012, 4, 142ra97. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Contreras, P.S.; Tapia, P.J.; González-Hódar, L.; Peluso, I.; Soldati, C.; Napolitano, G.; Matarese, M.; Heras, M.L.; Valls, C.; Martinez, A.; et al. c-Abl Inhibition Activates TFEB and Promotes Cellular Clearance in a Lysosomal Disorder. iScience 2020, 23, 101691. [Google Scholar] [CrossRef]
- Tsai, T.-H. Concurrent measurement of unbound genistein in the blood, brain and bile of anesthetized rats using microdialysis and its pharmacokinetic application. J. Chromatogr. A 2005, 1073, 317–322. [Google Scholar] [CrossRef]
- Friso, A.; Tomanin, R.; Salvalaio, M.; Scarpa, M. Genistein reduces glycosaminoglycan levels in a mouse model of muco-polysaccharidosis type II. Br. J. Pharmacol. 2010, 159, 1082–1091. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, K.H.; Dodsworth, C.; Paras, A.; Burton, B.K. High dose genistein aglycone therapy is safe in patients with muco-polysaccharidoses involving the central nervous system. Mol. Genet. Metab. 2013, 109, 382–385. [Google Scholar] [CrossRef]
- Malinová, V.; Węgrzyn, G.; Narajczyk, M. The use of elevated doses of genistein-rich soy extract in the gene expression-targeted isoflavone therapy for Sanfilippo disease patients. JIMD Rep. 2012, 5, 21–25. [Google Scholar] [PubMed] [Green Version]
- Moskot, M.; Jakóbkiewicz-Banecka, J.; Kloska, A.; Smolińska, E.; Mozolewski, P.; Malinowska, M.; Rychłowski, M.; Banecki, B.; Węgrzyn, G.; Gabig-Cimińska, M. Modulation of expression of genes involved in glycosaminoglycan metabolism and lysosome biogenesis by flavonoids. Sci. Rep. 2015, 5, 9378. [Google Scholar] [CrossRef] [Green Version]
- Pierzynowska, K.; Gaffke, L.; Hać, A.; Mantej, J.; Niedziałek, N.; Brokowska, J.; Węgrzyn, G. Correction of Huntington’s Disease Phenotype by Genistein-Induced Autophagy in the Cellular Model. NeuroMolecular Med. 2018, 20, 112–123. [Google Scholar] [CrossRef] [Green Version]
- Rega, L.R.; Polishchuk, E.; Montefusco, S.; Napolitano, G.; Tozzi, G.; Zhang, J.; Bellomo, F.; Taranta, A.; Pastore, A.; Polishchuk, R.; et al. Activation of the transcription factor EB rescues lysosomal abnormalities in cystinotic kidney cells. Kidney Int. 2016, 89, 862–873. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lu, F.; Liang, Q.; Abi-Mosleh, L.; Das, A.; De Brabander, J.K.; Goldstein, J.L.; Brown, M.S. Identification of NPC1 as the target of U18666A, an inhibitor of lysosomal cholesterol export and Ebola infection. eLife 2015, 4, e12177. [Google Scholar] [CrossRef] [PubMed]
- Di Malta, C.; Cinque, L.; Settembre, C. Transcriptional Regulation of Autophagy: Mechanisms and Diseases. Front. Cell Dev. Biol. 2019, 7, 114. [Google Scholar] [CrossRef] [PubMed]
- Sbano, L.; Bonora, M.; Marchi, S.; Baldassari, F.; Medina, D.L.; Ballabio, A.; Giorgi, C.; Pinton, P. TFEB-mediated increase in peripheral lysosomes regulates store-operated calcium entry. Sci. Rep. 2017, 7, 40797. [Google Scholar] [CrossRef] [PubMed]
- Kabeya, Y.; Mizushima, N.; Ueno, T.; Yamamoto, A.; Kirisako, T.; Noda, T.; Kominami, E.; Ohsumi, Y.; Yoshimori, T. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000, 19, 5720–5728. [Google Scholar] [CrossRef]
- Komatsu, M.; Kageyama, S.; Ichimura, Y. p62/SQSTM1/A170: Physiology and pathology. Pharmacol. Res. 2012, 66, 457–462. [Google Scholar] [CrossRef] [PubMed]
- Jiang, P.; Mizushima, N. LC3- and p62-based biochemical methods for the analysis of autophagy progression in mammalian cells. Methods 2015, 75, 13–18. [Google Scholar] [CrossRef]
- Yévenes, L.F.; Klein, A.; Castro, J.F.; Marín, T.; Leal, N.; Leighton, F.; Alvarez, A.R.; Zanlungo, S. Lysosomal vitamin E accumulation in Niemann–Pick type C disease. Biochim. Biophys. Acta (BBA)—Mol. Basis Dis. 2012, 1822, 150–160. [Google Scholar] [CrossRef] [Green Version]
- Moskot, M.; Montefusco, S.; Jakóbkiewicz-Banecka, J.; Mozolewski, P.; Węgrzyn, A.; Di Bernardo, D.; Węgrzyn, G.; Medina, D.L.; Ballabio, A.; Gabig-Cimińska, M. The Phytoestrogen Genistein Modulates Lysosomal Metabolism and Transcription Factor EB (TFEB) Activation. J. Biol. Chem. 2014, 289, 17054–17069. [Google Scholar] [CrossRef] [Green Version]
- Napolitano, G.; Ballabio, A. TFEB at a glance. J. Cell Sci. 2016, 129, 2475–2481. [Google Scholar] [CrossRef] [Green Version]
- Calderón, J.F.; Klein, A.D. Controversies on the potential therapeutic use of rapamycin for treating a lysosomal cholesterol storage disease. Mol. Genet. Metab. Rep. 2018, 15, 135–136. [Google Scholar] [CrossRef] [PubMed]
- Ramirez, C.M.; Liu, B.; Aqul, A.; Taylor, A.M.; Repa, J.J.; Turley, S.D.; Dietschy, J.M. Quantitative role of LAL, NPC2, and NPC1 in lysosomal cholesterol processing defined by genetic and pharmacological manipulations. J. Lipid Res. 2011, 52, 688–698. [Google Scholar] [CrossRef] [Green Version]
- Dai, S.; Dulcey, A.E.; Hu, X.; Wassif, C.A.; Porter, F.D.; Austin, C.P.; Ory, D.S.; Marugan, J.; Zheng, W. Me-thyl-β-cyclodextrin restores impaired autophagy flux in Niemann-Pick C1-deficient cells through activation of AMPK. Autophagy 2017, 13, 1435–1451. [Google Scholar] [CrossRef] [PubMed]
- Malik, B.R.; Maddison, D.C.; Smith, G.A.; Peters, O.M. Autophagic and endo-lysosomal dysfunction in neurodegenerative disease. Mol. Brain 2019, 12, 100. [Google Scholar] [CrossRef]
- Yu, Y.-C.; Hwang, T.-C. Curcumin and Genistein: The Combined Effects on Disease-associated CFTR Mutants and their Clinical Implications. Curr. Pharm. Des. 2013, 19, 3521–3528. [Google Scholar] [CrossRef] [Green Version]
- Pierzynowska, K.; Gaffke, L.; Jankowska, E.; Rintz, E.; Witkowska, J.; Wieczerzak, E.; Podlacha, M.; Węgrzyn, G. Proteasome Composition and Activity Changes in Cultured Fibroblasts Derived from Mucopolysaccharidoses Patients and Their Modula-tion by Genistein. Front. Cell Dev. Biol. 2020, 8, 540726. [Google Scholar] [CrossRef] [PubMed]
- Lim, C.; Bijvelds, M.; Nigg, A.; Schoonderwoerd, K.; Houtsmuller, A.; De Jonge, H.; Tilly, B. Cholesterol Depletion and Genistein as Tools to Promote F508delCFTR Retention at the Plasma Membrane. Cell. Physiol. Biochem. 2007, 20, 473–482. [Google Scholar] [CrossRef]
- Al-Nakkash, L.; Springsteel, M.F.; Kurth, M.J.; Nantz, M.H. Activation of CFTR by UCCF-029 and genistein. Bioorganic Med. Chem. Lett. 2008, 18, 3874–3877. [Google Scholar] [CrossRef]
- Schmidt, A.; Hughes, L.K.; Cai, Z.; Mendes, F.; Li, H.; Sheppard, D.N.; Amaral, M.D. Prolonged treatment of cells with genistein modulates the expression and function of the cystic fibrosis transmembrane conductance regulator. Br. J. Pharmacol. 2008, 153, 1311–1323. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Piotrowska, E.; Jakóbkiewicz-Banecka, J.; Tylki-Szymanska, A.; Liberek, A.; Maryniak, A.; Malinowska, M.; Czartoryska, B.; Puk, E.; Kloska, A.; Liberek, T.; et al. Genistin-rich soy isoflavone extract in substrate reduction therapy for Sanfilippo syndrome: An open-label, pilot study in 10 pediatric patients. Curr. Ther. Res. 2008, 69, 166–179. [Google Scholar] [CrossRef] [Green Version]
- Kingma, S.D.; Wagemans, T.; L, I.J.; Wijburg, F.A.; van Vlies, N. Genistein increases glycosaminoglycan levels in mu-copolysaccharidosis type I cell models. J. Inherit. Metab. Dis. 2014, 37, 813–821. [Google Scholar] [CrossRef]
- Kingma, S.D.K.; Wagemans, T.; Ijlst, L.; Seppen, J.; Gijbels, M.J.J.; Wijburg, F.A.; Van Vlies, N. Adverse Effects of Genistein in a Mucopolysaccharidosis Type I Mouse Model. JIMD Rep. 2015, 23, 77–83. [Google Scholar] [CrossRef] [Green Version]
- Delgadillo, V.; O’Callaghan, M.D.M.; Artuch, R.; Montero, R.; Pineda, M. Genistein supplementation in patients affected by Sanfilippo disease. J. Inherit. Metab. Dis. 2011, 34, 1039–1044. [Google Scholar] [CrossRef]
- De Ruijter, J.; Valstar, M.J.; Narajczyk, M.; Wegrzyn, G.; Kulik, W.; Ijlst, L.; Wagemans, T.; Van Der Wal, W.M.; Wijburg, F.A. Genistein in Sanfilippo disease: A randomized controlled crossover trial. Ann. Neurol. 2012, 71, 110–120. [Google Scholar] [CrossRef] [PubMed]
- Martini-Stoica, H.; Xu, Y.; Ballabio, A.; Zheng, H. The Autophagy–Lysosomal Pathway in Neurodegeneration: A TFEB Perspective. Trends Neurosci. 2016, 39, 221–234. [Google Scholar] [CrossRef] [Green Version]
- Pipalia, N.H.; Subramanian, K.; Mao, S.; Ralph, H.; Hutt, D.M.; Scott, S.M.; Balch, W.E.; Maxfield, F.R. Histone deacetylase inhibitors correct the cholesterol storage defect in most Niemann-Pick C1 mutant cells. J. Lipid Res. 2017, 58, 695–708. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Settembre, C.; Di Malta, C.; Polito, V.A.; Arencibia, M.G.; Vetrini, F.; Serkan, E.; Erdin, S.U.; Huynh, T.; Medina, D.; Colella, P.; et al. TFEB Links Autophagy to Lysosomal Biogenesis. Science 2011, 332, 1429–1433. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pfaffl, M.W. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001, 29, e45. [Google Scholar] [CrossRef]
- Talke, I.N.; Hanikenne, M.; Krämer, U. Zinc-Dependent Global Transcriptional Control, Transcriptional Deregulation, and Higher Gene Copy Number for Genes in Metal Homeostasis of the Hyperaccumulator Arabidopsis halleri. Plant Physiol. 2006, 142, 148–167. [Google Scholar] [CrossRef] [Green Version]
- Xu, M.; Liu, K.; Swaroop, M.; Porter, F.D.; Sidhu, R.; Finkes, S.; Ory, D.S.; Marugan, J.J.; Xiao, J.; Southall, N.; et al. δ-Tocopherol Reduces Lipid Accumulation in Niemann-Pick Type C1 and Wolman Cholesterol Storage Disorders*. J. Biol. Chem. 2012, 287, 39349–39360. [Google Scholar] [CrossRef] [Green Version]
- Ramakersab, C.; Ruijter, J.M.; Deprez, R.H.; Moorman, A.F. Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neurosci. Lett. 2003, 339, 62–66. [Google Scholar] [CrossRef]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Argüello, G.; Balboa, E.; Tapia, P.J.; Castro, J.; Yañez, M.J.; Mattar, P.; Pulgar, R.; Zanlungo, S. Genistein Activates Transcription Factor EB and Corrects Niemann–Pick C Phenotype. Int. J. Mol. Sci. 2021, 22, 4220. https://doi.org/10.3390/ijms22084220
Argüello G, Balboa E, Tapia PJ, Castro J, Yañez MJ, Mattar P, Pulgar R, Zanlungo S. Genistein Activates Transcription Factor EB and Corrects Niemann–Pick C Phenotype. International Journal of Molecular Sciences. 2021; 22(8):4220. https://doi.org/10.3390/ijms22084220
Chicago/Turabian StyleArgüello, Graciela, Elisa Balboa, Pablo J. Tapia, Juan Castro, María José Yañez, Pamela Mattar, Rodrigo Pulgar, and Silvana Zanlungo. 2021. "Genistein Activates Transcription Factor EB and Corrects Niemann–Pick C Phenotype" International Journal of Molecular Sciences 22, no. 8: 4220. https://doi.org/10.3390/ijms22084220