The Interactions of the 70 kDa Fragment of Cell Adhesion Molecule L1 with Topoisomerase 1, Peroxisome Proliferator-Activated Receptor γ and NADH Dehydrogenase (Ubiquinone) Flavoprotein 2 Are Involved in Gene Expression and Neuronal L1-Dependent Functions
Abstract
:1. Introduction
2. Results
2.1. L1-70 Interacts with TOP1, PPARγ and NDUFV2 via Its Intracellular Domain
2.2. TOP1, PPARγ and NDUFV2 Co-Localizes with L-70 in Cerebellar and Cortical Neurons
2.3. Reduction of TOP1, PPARγ and NDUFV2 Expression by siRNAs Reduces L1-Dependent Neurite Outgrowth
2.4. Disturbance of the L1/TOP1 and L1/PPARγ Interactions by the Cell-Penetrating L1 Peptide P4 Inhibits L1-Dependent Neurite Outgrowth of Cortical Neurons
2.5. Inhibition of Topoisomerase Activity Reduces L1-Dependent Neurite Outgrowth, and Neuronal Survival and Migration
2.6. Nrxn1 and Nlgn1 mRNA Levels Are Reduced by L1 siRNA and in L1-70-Deficient Mouse Brains
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. Reagents and Antibodies
4.3. ELISA
4.4. Cultures of Cerebellar and Cortical Neurons and of Cerebellar Explants
4.5. Proximity Ligation Assay and Immunostaining with Cerebellar and Cortical Neurons
4.6. Determination of Neurite Outgrowth, Neuronal Migration and Neuronal Survival
4.7. Immunorecipitation and Western Blot Analysis
4.8. qRT-PCR Analysis
4.9. Preparation of a Nuclear Protein Extract and Topoisomerase Activity Test
4.10. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Hortsch, M.; Nagaraj, K.; Mualla, R. The L1 family of cell adhesion molecules: A sickening number of mutations and protein functions. Adv. Neurobiol. 2014, 8, 195–229. [Google Scholar] [PubMed]
- Schäfer, M.K.; Altevogt, P. L1CAM malfunction in the nervous system and human carcinomas. Cell. Mol. Life Sci. 2010, 67, 2425–2437. [Google Scholar] [CrossRef] [PubMed]
- Sytnyk, V.; Leshchyns’ka, I.; Schachner, M. Neural cell adhesion molecules of the immunoglobulin superfamily regulate synapse formation, maintenance, and function. Trends Neurosci. 2017, 40, 295–308. [Google Scholar] [CrossRef] [PubMed]
- Poltorak, M.; Khoja, I.; Hemperly, J.J.; Williams, J.R.; El-Mallakh, R.; Freed, W.J. Disturbances in cell recognition molecules (N-CAM and L1 antigen) in the CSF of patients with schizophrenia. Exp. Neurol. 1995, 131, 266–272. [Google Scholar] [CrossRef]
- Wakabayashi, Y.; Uchida, S.; Funato, H.; Matsubara, T.; Watanuki, T.; Otsuki, K.; Fujimoto, M.; Nishida, A.; Watanabe, Y. State-dependent changes in the expression levels of NCAM-140 and L1 in the peripheral blood cells of bipolar disorders, but not in the major depressive disorders. Prog. Neuropsychopharmacol. Biol. Psychiatry 2008, 32, 1199–1205. [Google Scholar] [CrossRef]
- Strekalova, H.; Buhmann, C.; Kleene, R.; Eggers, C.; Saffell, J.; Hemperly, J.; Weiller, C.; Muller-Thomsen, T.; Schachner, M. Elevated levels of neural recognition molecule L1 in the cerebrospinal fluid of patients with Alzheimer disease and other dementia syndromes. Neurobiol. Aging 2006, 27, 1–9. [Google Scholar] [CrossRef]
- Kurumaji, A.; Nomoto, H.; Okano, T.; Toru, M. An association study between polymorphism of L1CAM gene and schizophrenia in a Japanese sample. Am. J. Med. Genet. 2001, 105, 99–104. [Google Scholar] [CrossRef]
- Djogo, N.; Jakovcevski, I.; Muller, C.; Lee, H.J.; Xu, J.C.; Jakovcevski, M.; Kugler, S.; Loers, G.; Schachner, M. Adhesion molecule L1 binds to amyloid beta and reduces Alzheimer’s disease pathology in mice. Neurobiol. Dis. 2013, 56, 104–115. [Google Scholar] [CrossRef]
- Yoo, M.; Carromeu, C.; Kwon, O.; Muotri, A.; Schachner, M. The L1 adhesion molecule normalizes neuritogenesis in Rett syndrome-derived neural precursor cells. Biochem. Biophys. Res. Commun. 2017, 494, 504–510. [Google Scholar] [CrossRef]
- Sauce, B.; Wass, C.; Netrakanti, M.; Saylor, J.; Schachner, M.; Matzel, L.D. Heterozygous L1-deficient mice express an autism-like phenotype. Behav. Brain Res. 2015, 292, 432–442. [Google Scholar] [CrossRef]
- Fransen, E.; Vits, L.; Van Camp, G.; Willems, P.J. The clinical spectrum of mutations in L1, a neuronal cell adhesion molecule. Am. J. Med. Genet. 1996, 64, 73–77. [Google Scholar] [CrossRef]
- Fransen, E.; D’Hooge, R.; Van Camp, G.; Verhoye, M.; Sijbers, J.; Reyniers, E.; Soriano, P.; Kamiguchi, H.; Willemsen, R.; Koekkoek, S.K.; et al. L1 knockout mice show dilated ventricles, vermis hypoplasia and impaired exploration patterns. Hum. Mol. Genet. 1998, 7, 999–1009. [Google Scholar] [CrossRef] [PubMed]
- Fransen, E.; Lemmon, V.; Van Camp, G.; Vits, L.; Coucke, P.; Willems, P.J. CRASH syndrome: Clinical spectrum of corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraparesis and hydrocephalus due to mutations in one single gene, L1. Eur. J. Hum. Genet. 1995, 3, 273–284. [Google Scholar] [CrossRef] [PubMed]
- Katidou, M.; Vidaki, M.; Strigini, M.; Karagogeos, D. The immunoglobulin superfamily of neuronal cell adhesion molecules: Lessons from animal models and correlation with human disease. Biotechnol. J. 2008, 3, 1564–1580. [Google Scholar] [CrossRef]
- Maness, P.F.; Schachner, M. Neural recognition molecules of the immunoglobulin superfamily: Signaling transducers of axon guidance and neuronal migration. Nat. Neurosci. 2007, 10, 19–26. [Google Scholar] [CrossRef]
- Law, J.W.; Lee, A.Y.; Sun, M.; Nikonenko, A.G.; Chung, S.K.; Dityatev, A.; Schachner, M.; Morellini, F. Decreased anxiety, altered place learning, and increased CA1 basal excitatory synaptic transmission in mice with conditional ablation of the neural cell adhesion molecule L1. J. Neurosci. 2003, 23, 10419–10432. [Google Scholar] [CrossRef] [Green Version]
- Barbin, G.; Aigrot, M.S.; Charles, P.; Foucher, A.; Grumet, M.; Schachner, M.; Zalc, B.; Lubetzki, C. Axonal cell-adhesion molecule L1 in CNS myelination. Neuron. Glia. Biol. 2004, 1, 65–72. [Google Scholar] [CrossRef]
- Guseva, D.; Angelov, D.N.; Irintchev, A.; Schachner, M. Ablation of adhesion molecule L1 in mice favours Schwann cell proliferation and functional recovery after peripheral nerve injury. Brain 2009, 132 Pt 8, 2180–2195. [Google Scholar] [CrossRef] [Green Version]
- Guseva, D.; Zerwas, M.; Xiao, M.F.; Jakovcevski, I.; Irintchev, A.; Schachner, M. Adhesion molecule L1 overexpressed under the control of the neuronal Thy-1 promoter improves myelination after peripheral nerve injury in adult mice. Exp. Neurol. 2011, 229, 339–352. [Google Scholar] [CrossRef]
- Luthl, A.; Laurent, J.P.; Figurov, A.; Muller, D.; Schachner, M. Hippocampal long-term potentiation and neural cell adhesion molecules L1 and NCAM. Nature 1994, 372, 777–779. [Google Scholar] [CrossRef]
- Jakovcevski, I.; Djogo, N.; Holters, L.S.; Szpotowicz, E.; Schachner, M. Transgenic overexpression of the cell adhesion molecule L1 in neurons facilitates recovery after mouse spinal cord injury. Neuroscience 2013, 252, 1–12. [Google Scholar] [CrossRef] [PubMed]
- Saghatelyan, A.K.; Nikonenko, A.G.; Sun, M.; Rolf, B.; Putthoff, P.; Kutsche, M.; Bartsch, U.; Dityatev, A.; Schachner, M. Reduced GABAergic transmission and number of hippocampal perisomatic inhibitory synapses in juvenile mice deficient in the neural cell adhesion molecule L1. Mol. Cell. Neurosci. 2004, 26, 191–203. [Google Scholar] [CrossRef] [PubMed]
- Ohyama, K.; Tan-Takeuchi, K.; Kutsche, M.; Schachner, M.; Uyemura, K.; Kawamura, K. Neural cell adhesion molecule L1 is required for fasciculation and routing of thalamocortical fibres and corticothalamic fibres. Neurosci. Res. 2004, 48, 471–475. [Google Scholar] [CrossRef] [PubMed]
- Lutz, D.; Kataria, H.; Kleene, R.; Loers, G.; Chaudhary, H.; Guseva, D.; Wu, B.; Jakovcevski, I.; Schachner, M. Myelin basic protein cleaves cell adhesion molecule L1 and improves regeneration after injury. Mol. Neurobiol. 2016, 53, 3360–3376. [Google Scholar] [CrossRef]
- Kleene, R.; Lutz, D.; Loers, G.; Bork, U.; Borgmeyer, U.; Hermans-Borgmeyer, I.; Schachner, M. Revisiting the proteolytic processing of cell adhesion molecule L1. J. Neurochem. 2021, 157, 1102–1117. [Google Scholar] [CrossRef]
- Lutz, D.; Loers, G.; Kleene, R.; Oezen, I.; Kataria, H.; Katagihallimath, N.; Braren, I.; Harauz, G.; Schachner, M. Myelin basic protein cleaves cell adhesion molecule L1 and promotes neuritogenesis and cell survival. J. Biol. Chem. 2014, 289, 13503–13518. [Google Scholar] [CrossRef] [Green Version]
- Lutz, D.; Sharaf, A.; Drexler, D.; Kataria, H.; Wolters-Eisfeld, G.; Brunne, B.; Kleene, R.; Loers, G.; Frotscher, M.; Schachner, M. Proteolytic cleavage of transmembrane cell adhesion molecule L1 by extracellular matrix molecule Reelin is important for mouse brain development. Sci. Rep. 2017, 7, 15268. [Google Scholar] [CrossRef] [Green Version]
- Lutz, D.; Wolters-Eisfeld, G.; Joshi, G.; Djogo, N.; Jakovcevski, I.; Schachner, M.; Kleene, R. Generation and nuclear translocation of sumoylated transmembrane fragment of cell adhesion molecule L1. J. Biol. Chem. 2012, 287, 17161–17175. [Google Scholar] [CrossRef] [Green Version]
- Lutz, D.; Wolters-Eisfeld, G.; Schachner, M.; Kleene, R. Cathepsin E generates a sumoylated intracellular fragment of the cell adhesion molecule L1 to promote neuronal and Schwann cell migration as well as myelination. J. Neurochem. 2014, 128, 713–724. [Google Scholar] [CrossRef]
- Kalus, I.; Schnegelsberg, B.; Seidah, N.G.; Kleene, R.; Schachner, M. The proprotein convertase PC5A and a metalloprotease are involved in the proteolytic processing of the neural adhesion molecule L1. J. Biol. Chem. 2003, 278, 10381–10388. [Google Scholar] [CrossRef]
- Mechtersheimer, S.; Gutwein, P.; Agmon-Levin, N.; Stoeck, A.; Oleszewski, M.; Riedle, S.; Postina, R.; Fahrenholz, F.; Fogel, M.; Lemmon, V.; et al. Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins. J. Cell. Biol. 2001, 155, 661–673. [Google Scholar] [CrossRef] [Green Version]
- Appel, F.; Holm, J.; Conscience, J.F.; Schachner, M. Several extracellular domains of the neural cell adhesion molecule L1 are involved in neurite outgrowth and cell body adhesion. J. Neurosci. 1993, 13, 4764–4775. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Holm, J.; Appel, F.; Schachner, M. Several extracellular domains of the neural cell adhesion molecule L1 are involved in homophilic interactions. J. Neurosci. Res. 1995, 42, 9–20. [Google Scholar] [CrossRef]
- Congiu, L.; Granato, V.; Loers, G.; Kleene, R.; Schachner, M. Mitochondrial and neuronal dysfunctions in L1 mutant mice. Int. J. Mol. Sci. 2022, 23, 4337. [Google Scholar] [CrossRef] [PubMed]
- Kraus, K.; Kleene, R.; Braren, I.; Loers, G.; Lutz, D.; Schachner, M. A fragment of adhesion molecule L1 is imported into mitochondria, and regulates mitochondrial metabolism and trafficking. J. Cell Sci. 2018, 131, jcs210500. [Google Scholar] [CrossRef] [Green Version]
- Kraus, K.; Kleene, R.; Henis, M.; Braren, I.; Kataria, H.; Sharaf, A.; Loers, G.; Schachner, M.; Lutz, D. A fragment of adhesion molecule L1 binds to nuclear receptors to regulate synaptic plasticity and motor coordination. Mol. Neurobiol. 2018, 55, 7164–7178. [Google Scholar] [CrossRef] [PubMed]
- Kleene, R.; Loers, G.; Castillo, G.; Schachner, M. Cell adhesion molecule L1 interacts with the chromo shadow domain of heterochromatin protein 1 isoforms alpha, beta, and via its intracellular domain. FASEB J. 2022, 36, e22074. [Google Scholar] [CrossRef]
- Loers, G.; Kleene, R.; Girbes Minguez, M.; Schachner, M. The cell adhesion molecule L1 interacts with methyl CpG binding protein 2 via its intracellular domain. Int. J. Mol. Sci. 2022, 23, 3554. [Google Scholar] [CrossRef]
- Girbes Minguez, M.; Wolters-Eisfeld, G.; Lutz, D.; Buck, F.; Schachner, M.; Kleene, R. The cell adhesion molecule L1 interacts with nuclear proteins via its intracellular domain. FASEB J. 2020, 34, 9869–9883. [Google Scholar] [CrossRef]
- Hu, J.; Lin, S.L.; Schachner, M. A fragment of cell adhesion molecule L1 reduces amyloid-beta plaques in a mouse model of Alzheimer’s disease. Cell Death Dis. 2022, 13, 48. [Google Scholar] [CrossRef]
- Kleene, R.; Loers, G.; Schachner, M. The KDET motif in the intracellular domain of the cell adhesion molecule L1 interacts with several nuclear, cytoplasmic, and mitochondrial proteins essential for neuronal functions. Int. J. Mol. Sci. 2023, 24, 932. [Google Scholar] [CrossRef]
- Chandra, V.; Huang, P.; Hamuro, Y.; Raghuram, S.; Wang, Y.; Burris, T.P.; Rastinejad, F. Structure of the intact PPAR-gamma-RXR- nuclear receptor complex on DNA. Nature 2008, 456, 350–356. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- King, I.F.; Yandava, C.N.; Mabb, A.M.; Hsiao, J.S.; Huang, H.S.; Pearson, B.L.; Calabrese, J.M.; Starmer, J.; Parker, J.S.; Magnuson, T.; et al. Topoisomerases facilitate transcription of long genes linked to autism. Nature 2013, 501, 58–62. [Google Scholar] [CrossRef] [Green Version]
- Mabb, A.M.; Simon, J.M.; King, I.F.; Lee, H.M.; An, L.K.; Philpot, B.D.; Zylka, M.J. Topoisomerase 1 regulates gene expression in neurons through cleavage complex-dependent and -independent mechanisms. PLoS ONE 2016, 11, e0156439. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, H.G.; Kishikawa, S.; Higgins, A.W.; Seong, I.S.; Donovan, D.J.; Shen, Y.; Lally, E.; Weiss, L.A.; Najm, J.; Kutsche, K.; et al. Disruption of neurexin 1 associated with autism spectrum disorder. Am. J. Hum. Genet. 2008, 82, 199–207. [Google Scholar] [CrossRef] [Green Version]
- Yan, J.; Noltner, K.; Feng, J.; Li, W.; Schroer, R.; Skinner, C.; Zeng, W.; Schwartz, C.E.; Sommer, S.S. Neurexin 1alpha structural variants associated with autism. Neurosci. Lett. 2008, 438, 368–370. [Google Scholar] [CrossRef] [PubMed]
- Nakanishi, M.; Nomura, J.; Ji, X.; Tamada, K.; Arai, T.; Takahashi, E.; Bucan, M.; Takumi, T. Functional significance of rare neuroligin 1 variants found in autism. PLoS Genet. 2017, 13, e1006940. [Google Scholar] [CrossRef] [Green Version]
- Tian, C.; Paskus, J.D.; Fingleton, E.; Roche, K.W.; Herring, B.E. Autism Spectrum Disorder/Intellectual Disability-associated mutations in Trio disrupt Neuroligin 1-mediated synaptogenesis. J. Neurosci. 2021, 41, 7768–7778. [Google Scholar] [CrossRef]
- Ruzzo, E.K.; Perez-Cano, L.; Jung, J.Y.; Wang, L.K.; Kashef-Haghighi, D.; Hartl, C.; Singh, C.; Xu, J.; Hoekstra, J.N.; Leventhal, O.; et al. Inherited and de novo genetic risk for autism impacts shared networks. Cell 2019, 178, 850–866.e26. [Google Scholar] [CrossRef] [Green Version]
- Egger, G.; Roetzer, K.M.; Noor, A.; Lionel, A.C.; Mahmood, H.; Schwarzbraun, T.; Boright, O.; Mikhailov, A.; Marshall, C.R.; Windpassinger, C.; et al. Identification of risk genes for autism spectrum disorder through copy number variation analysis in Austrian families. Neurogenetics 2014, 15, 117–127. [Google Scholar] [CrossRef]
- Douarre, C.; Sourbier, C.; Dalla Rosa, I.; Brata Das, B.; Redon, C.E.; Zhang, H.; Neckers, L.; Pommier, Y. Mitochondrial topoisomerase I is critical for mitochondrial integrity and cellular energy metabolism. PLoS ONE 2012, 7, e41094. [Google Scholar] [CrossRef] [Green Version]
- Zhang, H.; Barcelo, J.M.; Lee, B.; Kohlhagen, G.; Zimonjic, D.B.; Popescu, N.C.; Pommier, Y. Human mitochondrial topoisomerase I. Proc. Natl. Acad. Sci. USA 2001, 98, 10608–10613. [Google Scholar] [CrossRef] [Green Version]
- Kushwah, N.; Woeppel, K.; Dhawan, V.; Shi, D.; Cui, X.T. Effects of neuronal cell adhesion molecule L1 and nanoparticle surface modification on microglia. Acta Biomater. 2022, 149, 273–286. [Google Scholar] [CrossRef]
- Eles, J.R.; Vazquez, A.L.; Snyder, N.R.; Lagenaur, C.; Murphy, M.C.; Kozai, T.D.; Cui, X.T. Neuroadhesive L1 coating attenuates acute microglial attachment to neural electrodes as revealed by live two-photon microscopy. Biomaterials 2017, 113, 279–292. [Google Scholar] [CrossRef] [Green Version]
- Kolarcik, C.L.; Bourbeau, D.; Azemi, E.; Rost, E.; Zhang, L.; Lagenaur, C.F.; Weber, D.J.; Cui, X.T. In vivo effects of L1 coating on inflammation and neuronal health at the electrode-tissue interface in rat spinal cord and dorsal root ganglion. Acta Biomater. 2012, 8, 3561–3575. [Google Scholar] [CrossRef] [Green Version]
- Azemi, E.; Lagenaur, C.F.; Cui, X.T. The surface immobilization of the neural adhesion molecule L1 on neural probes and its effect on neuronal density and gliosis at the probe/tissue interface. Biomaterials 2011, 32, 681–692. [Google Scholar] [CrossRef] [Green Version]
- Südhof, T.C. Neuroligins and neurexins link synaptic function to cognitive disease. Nature 2008, 455, 903–911. [Google Scholar] [CrossRef] [Green Version]
- Betancur, C.; Sakurai, T.; Buxbaum, J.D. The emerging role of synaptic cell-adhesion pathways in the pathogenesis of autism spectrum disorders. Trends Neurosci. 2009, 32, 402–412. [Google Scholar] [CrossRef] [Green Version]
- Mabb, A.M.; Kullmann, P.H.; Twomey, M.A.; Miriyala, J.; Philpot, B.D.; Zylka, M.J. Topoisomerase 1 inhibition reversibly impairs synaptic function. Proc. Natl. Acad. Sci. USA 2014, 111, 17290–17295. [Google Scholar] [CrossRef] [Green Version]
- Fragola, G.; Mabb, A.M.; Taylor-Blake, B.; Niehaus, J.K.; Chronister, W.D.; Mao, H.; Simon, J.M.; Yuan, H.; Li, Z.; McConnell, M.J.; et al. Deletion of Topoisomerase 1 in excitatory neurons causes genomic instability and early onset neurodegeneration. Nat. Commun. 2020, 11, 1962. [Google Scholar] [CrossRef]
- Neale, B.M.; Kou, Y.; Liu, L.; Ma’ayan, A.; Samocha, K.E.; Sabo, A.; Lin, C.F.; Stevens, C.; Wang, L.S.; Makarov, V.; et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature 2012, 485, 242–245. [Google Scholar] [CrossRef] [Green Version]
- Iossifov, I.; Ronemus, M.; Levy, D.; Wang, Z.; Hakker, I.; Rosenbaum, J.; Yamrom, B.; Lee, Y.H.; Narzisi, G.; Leotta, A.; et al. De novo gene disruptions in children on the autistic spectrum. Neuron 2012, 74, 285–299. [Google Scholar] [CrossRef] [Green Version]
- Chen, S.; Jiang, Q.; Huang, P.; Hu, C.; Shen, H.; Schachner, M.; Zhao, W. The L1 cell adhesion molecule affects protein kinase D1 activity in the cerebral cortex in a mouse model of Alzheimer’s disease. Brain Res. Bull. 2020, 162, 141–150. [Google Scholar] [CrossRef]
- Hu, C.; Hu, J.; Meng, X.; Zhang, H.; Shen, H.; Huang, P.; Schachner, M.; Zhao, W. L1CAM beneficially inhibits histone deacetylase 2 expression under conditions of Alzheimer’s disease. Curr. Alzheimer Res. 2020, 17, 382–392. [Google Scholar] [CrossRef]
- Chen, T.; Wu, Q.; Zhang, Y.; Zhang, D. NDUFV2 regulates neuronal migration in the developing cerebral cortex through modulation of the multipolar-bipolar transition. Brain Res. 2015, 1625, 102–110. [Google Scholar] [CrossRef]
- Itoh, K.; Cheng, L.; Kamei, Y.; Fushiki, S.; Kamiguchi, H.; Gutwein, P.; Stoeck, A.; Arnold, B.; Altevogt, P.; Lemmon, V. Brain development in mice lacking L1-L1 homophilic adhesion. J. Cell Biol. 2004, 165, 145–154. [Google Scholar] [CrossRef]
- Jakeman, L.B.; Chen, Y.; Lucin, K.M.; McTigue, D.M. Mice lacking L1 cell adhesion molecule have deficits in locomotion and exhibit enhanced corticospinal tract sprouting following mild contusion injury to the spinal cord. Eur. J. Neurosci. 2006, 23, 1997–2011. [Google Scholar] [CrossRef]
- Tonosaki, M.; Itoh, K.; Umekage, M.; Kishimoto, T.; Yaoi, T.; Lemmon, V.P.; Fushiki, S. L1cam is crucial for cell locomotion and terminal translocation of the Soma in radial migration during murine corticogenesis. PLoS ONE 2014, 9, e86186. [Google Scholar] [CrossRef] [Green Version]
- Oruganty-Das, A.; Ng, T.; Udagawa, T.; Goh, E.L.; Richter, J.D. Translational control of mitochondrial energy production mediates neuron morphogenesis. Cell Metab. 2012, 16, 789–800. [Google Scholar] [CrossRef] [Green Version]
- Karry, R.; Klein, E.; Ben Shachar, D. Mitochondrial complex I subunits expression is altered in schizophrenia: A postmortem study. Biol. Psychiatry 2004, 55, 676–684. [Google Scholar] [CrossRef]
- Kim, S.H.; Vlkolinsky, R.; Cairns, N.; Fountoulakis, M.; Lubec, G. The reduction of NADH ubiquinone oxidoreductase 24- and 75-kDa subunits in brains of patients with Down syndrome and Alzheimer’s disease. Life Sci. 2001, 68, 2741–2750. [Google Scholar] [CrossRef]
- Nakatani, N.; Hattori, E.; Ohnishi, T.; Dean, B.; Iwayama, Y.; Matsumoto, I.; Kato, T.; Osumi, N.; Higuchi, T.; Niwa, S.; et al. Genome-wide expression analysis detects eight genes with robust alterations specific to bipolar I disorder: Relevance to neuronal network perturbation. Hum. Mol. Genet. 2006, 15, 1949–1962. [Google Scholar] [CrossRef] [Green Version]
- Hattori, N.; Yoshino, H.; Tanaka, M.; Suzuki, H.; Mizuno, Y. Genotype in the 24-kDa subunit gene (NDUFV2) of mitochondrial complex I and susceptibility to Parkinson disease. Genomics 1998, 49, 52–58. [Google Scholar] [CrossRef]
- Liu, H.Y.; Liao, P.C.; Chuang, K.T.; Kao, M.C. Mitochondrial targeting of human NADH dehydrogenase (ubiquinone) flavoprotein 2 (NDUFV2) and its association with early-onset hypertrophic cardiomyopathy and encephalopathy. J. Biomed. Sci. 2011, 18, 29. [Google Scholar] [CrossRef] [Green Version]
- Moutinho, M.; Landreth, G.E. Therapeutic potential of nuclear receptor agonists in Alzheimer’s disease. J. Lipid Res. 2017, 58, 1937–1949. [Google Scholar] [CrossRef] [Green Version]
- Geldmacher, D.S.; Fritsch, T.; McClendon, M.J.; Landreth, G. A randomized pilot clinical trial of the safety of pioglitazone in treatment of patients with Alzheimer disease. Arch. Neurol. 2011, 68, 45–50. [Google Scholar] [CrossRef] [Green Version]
- Gold, M.; Alderton, C.; Zvartau-Hind, M.; Egginton, S.; Saunders, A.M.; Irizarry, M.; Craft, S.; Landreth, G.; Linnamagi, U.; Sawchak, S. Rosiglitazone monotherapy in mild-to-moderate Alzheimer’s disease: Results from a randomized, double-blind, placebo-controlled phase III study. Dement. Geriatr. Cogn. Disord. 2010, 30, 131–146. [Google Scholar] [CrossRef] [Green Version]
- Landreth, G. Therapeutic use of agonists of the nuclear receptor PPARgamma in Alzheimer’s disease. Curr. Alzheimer Res. 2007, 4, 159–164. [Google Scholar] [CrossRef]
- Landreth, G. The immunology of Alzheimer’s disease: Prospects towards harnessing disease mechanisms for therapeutic ends. J. Neuroimmune Pharmacol. 2007, 2, 131–133. [Google Scholar] [CrossRef]
- Landreth, G.; Jiang, Q.; Mandrekar, S.; Heneka, M. PPARgamma agonists as therapeutics for the treatment of Alzheimer’s disease. Neurotherapeutics 2008, 5, 481–489. [Google Scholar] [CrossRef]
- Pisanu, A.; Lecca, D.; Mulas, G.; Wardas, J.; Simbula, G.; Spiga, S.; Carta, A.R. Dynamic changes in pro- and anti-inflammatory cytokines in microglia after PPAR-gamma agonist neuroprotective treatment in the MPTPp mouse model of progressive Parkinson’s disease. Neurobiol. Dis. 2014, 71, 280–291. [Google Scholar] [CrossRef] [PubMed]
- Shao, Z.Q.; Liu, Z.J. Neuroinflammation and neuronal autophagic death were suppressed via Rosiglitazone treatment: New evidence on neuroprotection in a rat model of global cerebral ischemia. J. Neurol. Sci. 2015, 349, 65–71. [Google Scholar] [CrossRef] [PubMed]
- Allahtavakoli, M.; Moloudi, R.; Arababadi, M.K.; Shamsizadeh, A.; Javanmardi, K. Delayed post ischemic treatment with Rosiglitazone attenuates infarct volume, neurological deficits and neutrophilia after embolic stroke in rat. Brain Res. 2009, 1271, 121–127. [Google Scholar] [CrossRef]
- Sundararajan, S.; Gamboa, J.L.; Victor, N.A.; Wanderi, E.W.; Lust, W.D.; Landreth, G.E. Peroxisome proliferator-activated receptor-gamma ligands reduce inflammation and infarction size in transient focal ischemia. Neuroscience 2005, 130, 685–696. [Google Scholar] [CrossRef]
- Zhao, X.; Strong, R.; Zhang, J.; Sun, G.; Tsien, J.Z.; Cui, Z.; Grotta, J.C.; Aronowski, J. Neuronal PPARgamma deficiency increases susceptibility to brain damage after cerebral ischemia. J. Neurosci. 2009, 29, 6186–6195. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Park, S.W.; Yi, J.H.; Miranpuri, G.; Satriotomo, I.; Bowen, K.; Resnick, D.K.; Vemuganti, R. Thiazolidinedione class of peroxisome proliferator-activated receptor gamma agonists prevents neuronal damage, motor dysfunction, myelin loss, neuropathic pain, and inflammation after spinal cord injury in adult rats. J. Pharmacol. Exp. Ther. 2007, 320, 1002–1012. [Google Scholar] [CrossRef]
- Meng, Q.Q.; Liang, X.J.; Wang, P.; Wang, X.P.; Yang, J.W.; Wu, Y.F.; Shen, H.Y. Rosiglitazone enhances the proliferation of neural progenitor cells and inhibits inflammation response after spinal cord injury. Neurosci. Lett. 2011, 503, 191–195. [Google Scholar] [CrossRef]
- Kataria, H.; Lutz, D.; Chaudhary, H.; Schachner, M.; Loers, G. Small molecule agonists of cell adhesion molecule L1 mimic L1 functions in vivo. Mol. Neurobiol. 2016, 53, 4461–4483. [Google Scholar] [CrossRef] [PubMed]
- He, X.; Knepper, M.; Ding, C.; Li, J.; Castro, S.; Siddiqui, M.; Schachner, M. Promotion of spinal cord regeneration by neural stem cell-secreted trimerized cell adhesion molecule L1. PLoS ONE 2012, 7, e46223. [Google Scholar] [CrossRef]
- Chen, J.; Bernreuther, C.; Dihne, M.; Schachner, M. Cell adhesion molecule l1-transfected embryonic stem cells with enhanced survival support regrowth of corticospinal tract axons in mice after spinal cord injury. J. Neurotrauma 2005, 22, 896–906. [Google Scholar] [CrossRef]
- Chen, J.; Wu, J.; Apostolova, I.; Skup, M.; Irintchev, A.; Kugler, S.; Schachner, M. Adeno-associated virus-mediated L1 expression promotes functional recovery after spinal cord injury. Brain 2007, 130 Pt 4, 954–969. [Google Scholar] [CrossRef] [Green Version]
- Cui, Y.F.; Xu, J.C.; Hargus, G.; Jakovcevski, I.; Schachner, M.; Bernreuther, C. Embryonic stem cell-derived L1 overexpressing neural aggregates enhance recovery after spinal cord injury in mice. PLoS ONE 2011, 6, e17126. [Google Scholar] [CrossRef] [Green Version]
- Guseva, D.; Loers, G.; Schachner, M. Function-triggering antibodies to the adhesion molecule L1 enhance recovery after injury of the adult mouse femoral nerve. PLoS ONE 2014, 9, e112984. [Google Scholar] [CrossRef] [Green Version]
- Lavdas, A.A.; Chen, J.; Papastefanaki, F.; Chen, S.; Schachner, M.; Matsas, R.; Thomaidou, D. Schwann cells engineered to express the cell adhesion molecule L1 accelerate myelination and motor recovery after spinal cord injury. Exp. Neurol. 2010, 221, 206–216. [Google Scholar] [CrossRef]
- Li, R.; Sahu, S.; Schachner, M. Phenelzine, a small organic compound mimicking the functions of cell adhesion molecule L1, promotes functional recovery after mouse spinal cord injury. Restor. Neurol. Neurosci. 2018, 36, 469–483. [Google Scholar] [CrossRef]
- Li, Y.; Huang, X.; An, Y.; Ren, F.; Yang, Z.Z.; Zhu, H.; Zhou, L.; He, X.; Schachner, M.; Xiao, Z.; et al. Cell recognition molecule L1 promotes embryonic stem cell differentiation through the regulation of cell surface glycosylation. Biochem. Biophys. Res. Commun. 2013, 440, 405–412. [Google Scholar] [CrossRef]
- Loers, G.; Cui, Y.F.; Neumaier, I.; Schachner, M.; Skerra, A. A Fab fragment directed against the neural cell adhesion molecule L1 enhances functional recovery after injury of the adult mouse spinal cord. Biochem. J. 2014, 460, 437–446. [Google Scholar] [CrossRef]
- Roonprapunt, C.; Huang, W.; Grill, R.; Friedlander, D.; Grumet, M.; Chen, S.; Schachner, M.; Young, W. Soluble cell adhesion molecule L1-Fc promotes locomotor recovery in rats after spinal cord injury. J. Neurotrauma 2003, 20, 871–882. [Google Scholar] [CrossRef]
- Sahu, S.; Zhang, Z.; Li, R.; Hu, J.; Shen, H.; Loers, G.; Shen, Y.; Schachner, M. A small organic compound mimicking the L1 cell adhesion molecule promotes functional recovery after spinal cord injury in zebrafish. Mol. Neurobiol. 2018, 55, 859–878. [Google Scholar] [CrossRef]
- Xu, J.; Hu, C.; Jiang, Q.; Pan, H.; Shen, H.; Schachner, M. Trimebutine, a small molecule mimetic agonist of adhesion molecule L1, contributes to functional recovery after spinal cord injury in mice. Dis. Model. Mech. 2017, 10, 1117–1128. [Google Scholar] [CrossRef]
- Xu, J.C.; Bernreuther, C.; Cui, Y.F.; Jakovcevski, I.; Hargus, G.; Xiao, M.F.; Schachner, M. Transplanted L1 expressing radial glia and astrocytes enhance recovery after spinal cord injury. J. Neurotrauma 2011, 28, 1921–1937. [Google Scholar] [CrossRef] [PubMed]
- Chi, O.Z.; Theis, T.; Kumar, S.; Chiricolo, A.; Liu, X.; Farooq, S.; Trivedi, N.; Young, W.; Schachner, M.; Weiss, H.R. Adhesion molecule L1 inhibition increases infarct size in cerebral ischemia-reperfusion without change in blood-brain barrier disruption. Neurol. Res. 2021, 43, 751–759. [Google Scholar] [CrossRef]
- Mirza, R.; Sharma, B. A selective peroxisome proliferator-activated receptor-gamma agonist benefited propionic acid induced autism-like behavioral phenotypes in rats by attenuation of neuroinflammation and oxidative stress. Chem. Biol. Interact. 2019, 311, 108758. [Google Scholar] [CrossRef]
- Mirza, R.; Sharma, B. Beneficial effects of pioglitazone, a selective peroxisome proliferator-activated receptor-gamma agonist in prenatal valproic acid-induced behavioral and biochemical autistic like features in Wistar rats. Int. J. Dev. Neurosci. 2019, 76, 6–16. [Google Scholar] [CrossRef]
- Ghosh, S.; Patel, N.; Rahn, D.; McAllister, J.; Sadeghi, S.; Horwitz, G.; Berry, D.; Wang, K.X.; Swerdlow, R.H. The thiazolidinedione pioglitazone alters mitochondrial function in human neuron-like cells. Mol. Pharmacol. 2007, 71, 1695–1702. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Miglio, G.; Rosa, A.C.; Rattazzi, L.; Collino, M.; Lombardi, G.; Fantozzi, R. PPARgamma stimulation promotes mitochondrial biogenesis and prevents glucose deprivation-induced neuronal cell loss. Neurochem. Int. 2009, 55, 496–504. [Google Scholar] [CrossRef] [PubMed]
- Zolezzi, J.M.; Silva-Alvarez, C.; Ordenes, D.; Godoy, J.A.; Carvajal, F.J.; Santos, M.J.; Inestrosa, N.C. Peroxisome proliferator-activated receptor (PPAR) gamma and PPARalpha agonists modulate mitochondrial fusion-fission dynamics: Relevance to reactive oxygen species (ROS)-related neurodegenerative disorders? PLoS ONE 2013, 8, e64019. [Google Scholar] [CrossRef] [Green Version]
- Corona, J.C.; Duchen, M.R. PPARgamma as a therapeutic target to rescue mitochondrial function in neurological disease. Free Radic. Biol. Med. 2016, 100, 153–163. [Google Scholar] [CrossRef] [Green Version]
- Chauhan, A.; Gu, F.; Chauhan, V. Mitochondrial respiratory chain defects in autism and other neurodevelopmental disorders. J. Pediatr. Biochem. 2012, 2, 181–191. [Google Scholar] [CrossRef]
- Kilkenny, C.; Browne, W.; Cuthill, I.C.; Emerson, M.; Altman, D.G. Animal research: Reporting in vivo experiments: The ARRIVE guidelines. J. Gene Med. 2010, 12, 561–563. [Google Scholar] [CrossRef]
- Appel, F.; Holm, J.; Conscience, J.F.; von Bohlen und Halbach, F.; Faissner, A.; James, P.; Schachner, M. Identification of the border between fibronectin type III homologous repeats 2 and 3 of the neural cell adhesion molecule L1 as a neurite outgrowth promoting and signal transducing domain. J. Neurobiol. 1995, 28, 297–312. [Google Scholar] [CrossRef] [PubMed]
- Kleene, R.; Cassens, C.; Bahring, R.; Theis, T.; Xiao, M.F.; Dityatev, A.; Schafer-Nielsen, C.; Doring, F.; Wischmeyer, E.; Schachner, M. Functional consequences of the interactions among the neural cell adhesion molecule NCAM, the receptor tyrosine kinase TrkB, and the inwardly rectifying K+ channel KIR3.3. J. Biol. Chem. 2010, 285, 28968–28979. [Google Scholar] [CrossRef] [PubMed]
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Loers, G.; Kleene, R.; Bork, U.; Schachner, M. The Interactions of the 70 kDa Fragment of Cell Adhesion Molecule L1 with Topoisomerase 1, Peroxisome Proliferator-Activated Receptor γ and NADH Dehydrogenase (Ubiquinone) Flavoprotein 2 Are Involved in Gene Expression and Neuronal L1-Dependent Functions. Int. J. Mol. Sci. 2023, 24, 2097. https://doi.org/10.3390/ijms24032097
Loers G, Kleene R, Bork U, Schachner M. The Interactions of the 70 kDa Fragment of Cell Adhesion Molecule L1 with Topoisomerase 1, Peroxisome Proliferator-Activated Receptor γ and NADH Dehydrogenase (Ubiquinone) Flavoprotein 2 Are Involved in Gene Expression and Neuronal L1-Dependent Functions. International Journal of Molecular Sciences. 2023; 24(3):2097. https://doi.org/10.3390/ijms24032097
Chicago/Turabian StyleLoers, Gabriele, Ralf Kleene, Ute Bork, and Melitta Schachner. 2023. "The Interactions of the 70 kDa Fragment of Cell Adhesion Molecule L1 with Topoisomerase 1, Peroxisome Proliferator-Activated Receptor γ and NADH Dehydrogenase (Ubiquinone) Flavoprotein 2 Are Involved in Gene Expression and Neuronal L1-Dependent Functions" International Journal of Molecular Sciences 24, no. 3: 2097. https://doi.org/10.3390/ijms24032097