{"id":604240,"date":"2024-06-02T20:00:00","date_gmt":"2024-06-03T00:00:00","guid":{"rendered":"https:\/\/platohealth.ai\/advances-and-challenges-in-modeling-inherited-peripheral-neuropathies-using-ipscs-experimental-molecular-medicine\/"},"modified":"2024-06-03T00:26:24","modified_gmt":"2024-06-03T04:26:24","slug":"advances-and-challenges-in-modeling-inherited-peripheral-neuropathies-using-ipscs-experimental-molecular-medicine","status":"publish","type":"post","link":"https:\/\/platohealth.ai\/advances-and-challenges-in-modeling-inherited-peripheral-neuropathies-using-ipscs-experimental-molecular-medicine\/","title":{"rendered":"Advances and challenges in modeling inherited peripheral neuropathies using iPSCs – Experimental & Molecular Medicine","gt_translate_keys":[{"key":"rendered","format":"text"}]},"content":{"rendered":"
Baets, J., De Jonghe, P. & Timmerman, V. Recent advances in Charcot\u2013Marie\u2013Tooth disease. Curr. Opin. Neurol.<\/i> 27<\/b>, 532\u2013540 (2014).<\/p>\n
Article<\/a> Pisciotta, C. & Shy, M. E. Neuropathy. Handb. Clin. Neurol<\/i> 148, 653\u2013665 (2018).<\/p>\n<\/li>\n Saporta, M. A. & Shy, M. E. Inherited peripheral neuropathies. Neurol. Clin.<\/i> 31<\/b>, 597\u2013619 (2013).<\/p>\n Article<\/a> Adams, D. et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N. Engl. J. Med.<\/i> 379<\/b>, 11\u201321 (2018).<\/p>\n Article<\/a> Benson, M. D. et al. Inotersen treatment for patients with hereditary transthyretin amyloidosis. N. Engl. J. Med.<\/i> 379<\/b>, 22\u201331 (2018).<\/p>\n Article<\/a> Passage, E. et al. Ascorbic acid treatment corrects the phenotype of a mouse model of Charcot-Marie-Tooth disease. Nat. Med.<\/i> 10<\/b>, 396\u2013401 (2004).<\/p>\n Article<\/a> Lewis, R. A. High-dosage ascorbic acid treatment in Charcot-Marie-Tooth disease type 1A. JAMA Neurol.<\/i> 70<\/b>, 981\u2013987 (2013).<\/p>\n Article<\/a> Pareyson, D. et al. Ascorbic acid in Charcot\u2013Marie\u2013Tooth disease type 1A (CMT-TRIAAL and CMT-TRAUK): a double-blind randomised trial. Lancet Neurol.<\/i> 10<\/b>, 320\u2013328 (2011).<\/p>\n Article<\/a> Verhamme, C. et al. Oral high dose ascorbic acid treatment for one year in young CMT1A patients: a randomised, double-blind, placebo-controlled phase II trial. BMC Med.<\/i> 7<\/b>, 70 (2009).<\/p>\n Article<\/a> Burns, J. et al. Ascorbic acid for Charcot\u2013Marie\u2013Tooth disease type 1A in children: a randomised, double-blind, placebo-controlled, safety and efficacy trial. Lancet Neurol.<\/i> 8<\/b>, 537\u2013544 (2009).<\/p>\n Article<\/a> Garofalo, K. et al. Oral l-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. J. Clin. Investig.<\/i> 121<\/b>, 4735\u20134745 (2011).<\/p>\n Article<\/a> Fridman, V. et al. Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1. Neurology<\/i> 92<\/b>, 359 (2019).<\/p>\n Article<\/a> Colman, A. Profile of John Gurdon and Shinya Yamanaka, 2012 Nobel Laureates in medicine or physiology. Proc. Natl Acad. Sci. USA<\/i> 110<\/b>, 5740\u20135741 (2013).<\/p>\n Article<\/a> Lee, G. et al. Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature<\/i> 461<\/b>, 402\u2013406 (2009).<\/p>\n Article<\/a> Saporta, M. A. et al. Axonal Charcot-Marie-Tooth disease patient-derived motor neurons demonstrate disease-specific phenotypes including abnormal electrophysiological properties. Exp. Neurol.<\/i> 263<\/b>, 190\u2013199 (2015).<\/p>\n Article<\/a> Harschnitz, O. et al. Autoantibody pathogenicity in a multifocal motor neuropathy induced pluripotent stem cell-derived model. Ann. Neurol.<\/i> 80<\/b>, 71\u201388 (2016).<\/p>\n Article<\/a> Perez-Siles, G. et al. Energy metabolism and mitochondrial defects in X-linked Charcot-Marie-Tooth (CMTX6) iPSC-derived motor neurons with the p.R158H PDK3 mutation. Sci. Rep.<\/i> 10<\/b>, 9262 (2020).<\/p>\n Article<\/a> Cutrupi, A. N. et al. Novel gene\u2013intergenic fusion involving ubiquitin E3 ligase UBE3C causes distal hereditary motor neuropathy. Brain<\/i> 146<\/b>, 880\u2013897 (2023).<\/p>\n Article<\/a> Maury, Y. et al. Combinatorial analysis of developmental cues efficiently converts human pluripotent stem cells into multiple neuronal subtypes. Nat. Biotechnol.<\/i> 33<\/b>, 89\u201396 (2015).<\/p>\n Article<\/a> Guo, W. et al. HDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients. Nat. Commun.<\/i> 8<\/b>, 861 (2017).<\/p>\n Article<\/a> Van Lent, J. et al. Induced pluripotent stem cell-derived motor neurons of CMT type 2 patients reveal progressive mitochondrial dysfunction. Brain<\/i> 144<\/b>, 2471\u20132485 (2021).<\/p>\n Article<\/a> Faye, P.-A. et al. Optimized protocol to generate spinal motor neuron cells from induced pluripotent stem cells from Charcot Marie Tooth patients. Brain Sci.<\/i> 10<\/b>, 407 (2020).<\/p>\n Article<\/a> LaVaute, T. M. et al. Regulation of neural specification from human embryonic. Stem Cells BMP Fgf. Stem Cells<\/i> 27<\/b>, 1741\u20131749 (2009).<\/p>\n CAS<\/a> Miressi, F. et al. GDAP1 involvement in mitochondrial function and oxidative stress, investigated in a Charcot-Marie-Tooth model of hiPSCs-derived motor neurons. Biomedicines<\/i> 9<\/b>, 945 (2021).<\/p>\n Article<\/a> Feliciano, C. M. et al. Allele-specific gene editing rescues pathology in a human model of Charcot-Marie-Tooth disease type 2E. Front Cell Dev. Biol.<\/i> 9<\/b>, 723023 (2021).<\/p>\n Article<\/a> Limone, F. et al. Efficient generation of lower induced motor neurons by coupling Ngn2 expression with developmental cues. Cell Rep.<\/i> 42<\/b>, 111896 (2023).<\/p>\n Article<\/a> Perez-Siles, G. et al. Modelling the pathogenesis of X-linked distal hereditary motor neuropathy using patient-derived iPSCs. Dis. Model Mech.<\/i> 13<\/b>, dmm041541 (2020).<\/p>\n Article<\/a> Clark, A. J. et al. An iPSC model of hereditary sensory neuropathy-1 reveals L-serine-responsive deficits in neuronal ganglioside composition and axoglial interactions. Cell Rep. Med.<\/i> 2<\/b>, 100345 (2021).<\/p>\n Article<\/a> Romano, R. et al. Alteration of the late endocytic pathway in Charcot\u2013Marie\u2013Tooth type 2B disease. Cell. Mol. Life Sci.<\/i> 78<\/b>, 351\u2013372 (2021).<\/p>\n Article<\/a> Chambers, S. M. et al. Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors. Nat. Biotechnol.<\/i> 30<\/b>, 715\u2013720 (2012).<\/p>\n Article<\/a> Schrenk-Siemens, K. et al. PIEZO2 is required for mechanotransduction in human stem cell\u2013derived touch receptors. Nat. Neurosci.<\/i> 18<\/b>, 10\u201316 (2015).<\/p>\n Article<\/a> Middleton, S. J. et al. Studying human nociceptors: from fundamentals to clinic. Brain<\/i> 144<\/b>, 1312\u20131335 (2021).<\/p>\n Article<\/a> Nickolls, A. R. et al. Transcriptional programming of human mechanosensory neuron subtypes from pluripotent stem cells. Cell Rep.<\/i> 30<\/b>, 932\u2013946 (2020).<\/p>\n Article<\/a> Alshawaf, A. J. et al. Phenotypic and functional characterization of peripheral sensory neurons derived from human embryonic stem cells. Sci. Rep.<\/i> 8<\/b>, 603 (2018).<\/p>\n Article<\/a> Saito-Diaz, K., Street, J. R., Ulrichs, H. & Zeltner, N. Derivation of peripheral nociceptive, mechanoreceptive, and proprioceptive sensory neurons from the same culture of human pluripotent stem cells. Stem Cell Rep.<\/i> 16<\/b>, 446\u2013457 (2021).<\/p>\n Article<\/a> Ernsberger, U. Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia. Cell Tissue Res.<\/i> 336<\/b>, 349\u2013384 (2009).<\/p>\n Article<\/a> Zeidler, M. et al. NOCICEPTRA: gene and microRNA signatures and their trajectories characterizing human iPSC\u2010derived nociceptor maturation. Adv. Sci.<\/i> 8<\/b>, 2102354 (2021).<\/p>\n Article<\/a> Eberhardt, E. et al. Pattern of functional TTX-resistant sodium channels reveals a developmental stage of human iPSC- and ESC-derived nociceptors. Stem Cell Rep.<\/i> 5<\/b>, 305\u2013313 (2015).<\/p>\n Article<\/a> Deng, T. et al. Scalable generation of sensory neurons from human pluripotent stem cells. Stem Cell Rep.<\/i> 18<\/b>, 1030\u20131047 (2023).<\/p>\n Article<\/a> Oh, Y. et al. Functional coupling with cardiac muscle promotes maturation of hPSC-derived sympathetic neurons. Cell Stem Cell<\/i> 19<\/b>, 95\u2013106 (2016).<\/p>\n Article<\/a> Kirino, K., Nakahata, T., Taguchi, T. & Saito, M. K. Efficient derivation of sympathetic neurons from human pluripotent stem cells with a defined condition. Sci. Rep.<\/i> 8<\/b>, 12865 (2018).<\/p>\n Article<\/a> Frith, T. J. et al. Human axial progenitors generate trunk neural crest cells in vitro. Elife<\/i> 7<\/b>, e35786 (2018).<\/p>\n Article<\/a> Wu, H.-F. et al. Norepinephrine transporter defects lead to sympathetic hyperactivity in Familial Dysautonomia models. Nat. Commun.<\/i> 13<\/b>, 7032 (2022).<\/p>\n Article<\/a> Wu, H.-F. et al. Parasympathetic neurons derived from human pluripotent stem cells model human diseases and development. Cell Stem Cell. S1934\u20135909<\/b>, 00092\u20134. https:\/\/pubmed.ncbi.nlm.nih.gov\/38608707\/<\/a> (2024) Online ahead of print.<\/p>\n<\/li>\n Muhammad, A. et al. Cell transplantation strategies for acquired and inherited disorders of peripheral myelin. Ann. Clin. Transl. Neurol.<\/i> 5<\/b>, 186\u2013200 (2018).<\/p>\n Article<\/a> Huang, Z., Powell, R., Kankowski, S., Phillips, J. B. & Haastert-Talini, K. Culture conditions for human induced pluripotent stem cell-derived Schwann cells: a two-centre study. Int. J. Mol. Sci.<\/i> 24<\/b>, 5366 (2023).<\/p>\n Article<\/a> Majd, H. et al. Deriving Schwann cells from hPSCs enables disease modeling and drug discovery for diabetic peripheral neuropathy. Cell Stem Cell<\/i> 30<\/b>, 632\u2013647 (2023).<\/p>\n Article<\/a> Kim, H.-S., Kim, J. Y., Song, C. L., Jeong, J. E. & Cho, Y. S. Directly induced human Schwann cell precursors as a valuable source of Schwann cells. Stem Cell Res. Ther.<\/i> 11<\/b>, 257 (2020).<\/p>\n Article<\/a> Kim, H.-S. et al. Schwann cell precursors from human pluripotent stem cells as a potential therapeutic target for Myelin repair. Stem Cell Rep.<\/i> 8<\/b>, 1714\u20131726 (2017).<\/p>\n Article<\/a> Mukherjee-Clavin, B. et al. Comparison of three congruent patient-specific cell types for the modelling of a human genetic Schwann-cell disorder. Nat. Biomed. Eng.<\/i> 3<\/b>, 571\u2013582 (2019).<\/p>\n Article<\/a> Prior, R. et al. Defective Schwann cell lipid metabolism alters plasma membrane dynamics in Charcot-Marie-Tooth disease 1A. Preprint at bioRxiv<\/i> https:\/\/doi.org\/10.1101\/2023.04.02.535224<\/a> (2023).<\/p>\n<\/li>\n Adameyko, I. et al. Schwann cell precursors from nerve innervation are a cellular origin of melanocytes in skin. Cell<\/i> 139<\/b>, 366\u2013379 (2009).<\/p>\n Article<\/a> Paratore, C., Goerich, D. E., Suter, U., Wegner, M. & Sommer, L. Survival and glial fate acquisition of neural crest cells are regulated by an interplay between the transcription factor Sox10 and extrinsic combinatorial signaling. Development<\/i> 128<\/b>, 3949\u20133961 (2001).<\/p>\n Article<\/a> Britsch, S. et al. The transcription factor Sox10 is a key regulator of peripheral glial development. Genes Dev.<\/i> 15<\/b>, 66\u201378 (2001).<\/p>\n Article<\/a> Dyachuk, V. et al. Parasympathetic neurons originate from nerve-associated peripheral glial progenitors. Science<\/i> 345<\/b>, 82\u201387 (2014).<\/p>\n Article<\/a> Kastriti, M. E. et al. Schwann cell precursors represent a neural crest\u2010like state with biased multipotency. EMBO J.<\/i> 41<\/b>, 108780 (2022).<\/p>\n Article<\/a> Xie, M. et al. Schwann cell precursors contribute to skeletal formation during embryonic development in mice and zebrafish. Proc. Natl Acad. Sci. USA<\/i> 116<\/b>, 15068\u201315073 (2019).<\/p>\n Article<\/a> Jessen, K. R. & Mirsky, R. Schwann cell precursors; multipotent glial cells in embryonic nerves. Front. Mol. Neurosci.<\/i> 12<\/b>, 69 (2019).<\/p>\n Article<\/a> Jessen, K. R. & Mirsky, R. The origin and development of glial cells in peripheral nerves. Nat. Rev. Neurosci.<\/i> 6<\/b>, 671\u2013682 (2005).<\/p>\n Article<\/a> Stassart, R. M. & Woodhoo, A. Axo\u2010glial interaction in the injured PNS. Dev. Neurobiol.<\/i> 81<\/b>, 490\u2013506 (2021).<\/p>\n Article<\/a> Nitzan, E., Pfaltzgraff, E. R., Labosky, P. A. & Kalcheim, C. Neural crest and Schwann cell progenitor-derived melanocytes are two spatially segregated populations similarly regulated by Foxd3. Proc. Natl Acad. Sci. USA<\/i> 110<\/b>, 12709\u201312714 (2013).<\/p>\n Article<\/a> Van Raamsdonk, C. D. & Deo, M. Links between Schwann cells and melanocytes in development and disease. Pigment Cell Melanoma Res.<\/i> 26<\/b>, 634\u2013645 (2013).<\/p>\n Article<\/a> Colombo, S. et al. Stabilization of \u03b2-catenin promotes melanocyte specification at the expense of the Schwann cell lineage. Development<\/i> 149<\/b>, dev194407 (2022).<\/p>\n Article<\/a> Marathe, H. G. et al. BRG1 interacts with SOX10 to establish the melanocyte lineage and to promote differentiation. Nucleic Acids Res.<\/i> 45<\/b>, 6442\u20136458 (2017).<\/p>\n Article<\/a> Slutsky, S. G., Kamaraju, A. K., Levy, A. M., Chebath, J. & Revel, M. Activation of Myelin genes during transdifferentiation from melanoma to glial cell phenotype. J. Biol. Chem.<\/i> 278<\/b>, 8960\u20138968 (2003).<\/p>\n Article<\/a> Rambow, F. et al. New functional signatures for understanding melanoma biology from tumor cell lineage-specific analysis. Cell Rep.<\/i> 13<\/b>, 840\u2013853 (2015).<\/p>\n Article<\/a> Smith, A. et al. HDAC6 inhibition corrects electrophysiological and axonal transport deficits in a human stem cell\u2010based model of Charcot\u2010Marie\u2010Tooth disease (type 2D). Adv. Biol.<\/i> 6<\/b>, 2101308 (2022).<\/p>\n Article<\/a> Kennerson, M. L. et al. Missense mutations in the copper transporter gene ATP7A cause X-linked distal hereditary motor neuropathy. Am. J. Hum. Genet.<\/i> 86<\/b>, 343\u2013352 (2010).<\/p>\n Article<\/a> Zhu, Y. et al. Sorbitol reduction via govorestat ameliorates synaptic dysfunction and neurodegeneration in sorbitol dehydrogenase deficiency. JCI Insight<\/i> 8<\/b>, e164954 (2023).<\/p>\n Article<\/a> McDermott, L. A. et al. Defining the functional role of NaV1.7 in human nociception. Neuron<\/i> 101<\/b>, 905\u2013919 (2019).<\/p>\n Article<\/a> Haidar, M. et al. Neuropathy-causing mutations in HSPB1 impair autophagy by disturbing the formation of SQSTM1\/p62 bodies. Autophagy<\/i> 15<\/b>, 1051\u20131068 (2019).<\/p>\n Article<\/a> Alderson, T. R. et al. A weakened interface in the P182L variant of HSP27 associated with severe Charcot-Marie-Tooth neuropathy causes aberrant binding to interacting proteins. EMBO J.<\/i> 40<\/b>, 103811 (2021).<\/p>\n Article<\/a> Maciel, R., Correa, R., Bosso Taniguchi, J., Prufer Araujo, I. & Saporta, M. A. Human tridimensional neuronal cultures for phenotypic drug screening in inherited peripheral neuropathies. Clin. Pharm. Ther.<\/i> 107<\/b>, 1231\u20131239 (2020).<\/p>\n Article<\/a> Kenvin, S. et al. Threshold of heteroplasmic truncating MT-ATP6 mutation in reprogramming, Notch hyperactivation and motor neuron metabolism. Hum. Mol. Genet.<\/i> 31<\/b>, 958\u2013974 (2022).<\/p>\n Article<\/a> Carri\u00f3, M. et al. Reprogramming captures the genetic and tumorigenic properties of neurofibromatosis type 1 plexiform neurofibromas. Stem Cell Rep.<\/i> 12<\/b>, 411\u2013426 (2019).<\/p>\n Article<\/a> Cutrupi, A. N., Brewer, M. H., Nicholson, G. A. & Kennerson, M. L. Structural variations causing inherited peripheral neuropathies: a paradigm for understanding genomic organization, chromatin interactions, and gene dysregulation. Mol. Genet. Genom. Med.<\/i> 6<\/b>, 422\u2013433 (2018).<\/p>\n Article<\/a> Sudmant, P. H. et al. An integrated map of structural variation in 2,504 human genomes. Nature<\/i> 526<\/b>, 75\u201381 (2015).<\/p>\n Article<\/a> Drew, A. P., Cutrupi, A. N., Brewer, M. H., Nicholson, G. A. & Kennerson, M. L. A 1.35\u2009Mb DNA fragment is inserted into the DHMN1 locus on chromosome 7q34\u2013q36.2. Hum. Genet.<\/i> 135<\/b>, 1269\u20131278 (2016).<\/p>\n Article<\/a> Brewer, M. H. et al. Whole genome sequencing identifies a 78\u2009kb insertion from chromosome 8 as the cause of Charcot-Marie-Tooth neuropathy CMTX3. PLoS Genet.<\/i> 12<\/b>, 1006177 (2016).<\/p>\n Article<\/a> D’ydewalle, C. et al. HDAC6 inhibitors reverse axonal loss in a mouse model of mutant HSPB1-induced Charcot-Marie-Tooth disease. Nat. Med.<\/i> 17<\/b>, 968\u2013974 (2011).<\/p>\n Article<\/a> Kalmar, B. et al. Mitochondrial deficits and abnormal mitochondrial retrograde axonal transport play a role in the pathogenesis of mutant Hsp27-induced Charcot Marie Tooth disease. Hum. Mol. Genet.<\/i> 26<\/b>, 3313\u20133326 (2017).<\/p>\n Article<\/a> Baloh, R. H., Schmidt, R. E., Pestronk, A. & Milbrandt, J. Altered Axonal Mitochondrial Transport In The Pathogenesis of Charcot-Marie-Tooth disease from mitofusin 2 mutations. J. Neurosci.<\/i> 27<\/b>, 422\u2013430 (2007).<\/p>\n Article<\/a> Alecu, I. et al. Localization of 1-deoxysphingolipids to mitochondria induces mitochondrial dysfunction. J. Lipid Res.<\/i> 58<\/b>, 42\u201359 (2017).<\/p>\n Article<\/a> Adriaenssens, E. et al. Small heat shock proteins operate as molecular chaperones in the mitochondrial intermembrane space. Nat. Cell Biol.<\/i>
\n CAS<\/a>
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n PubMed Central<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n
\n CAS<\/a>
\n PubMed<\/a>
\n
\n Google Scholar<\/a> \n <\/p>\n<\/li>\n