Activation of the Anti-Aging and Cognition-Enhancing Gene Klotho by CRISPR-dCas9 Transcriptional Effector Complex

Abraham CR, Chen C, Cuny GD, Glicksman MA, Zeldich E (2012) Small-molecule Klotho enhancers as novel treatment of neurodegeneration. Future Med Chem 4(13):1671–1679. https://doi.org/10.4155/fmc.12.134

Abraham CR, Mullen PC, Tucker-Zhou T, Chen CD, Zeldich E (2016) Klotho is a neuroprotective and cognition-enhancing protein. Vitam Horm 101:215–238. https://doi.org/10.1016/bs.vh.2016.02.004

Bloch L, Sineshchekova O, Reichenbach D, Reiss K, Saftig P, Kuro-o M, Kaether C (2009) Klotho is a substrate for alpha-, beta- and gamma-secretase. FEBS Lett 583(19):3221–3224. https://doi.org/10.1016/j.febslet.2009.09.009

Chen CD, Li H, Liang J, Hixson K, Zeldich E, Abraham CR (2015) The anti-aging and tumor suppressor protein Klotho enhances differentiation of a human oligodendrocytic hybrid cell line. J Mol Neurosci : MN 55(1):76–90. https://doi.org/10.1007/s12031-014-0336-1

Chen CD, Podvin S, Gillespie E, Leeman SE, Abraham CR (2007) Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17. Proc Natl Acad Sci U S A 104(50):19796–19801. https://doi.org/10.1073/pnas.0709805104

Chen CD, Sloane JA, Li H, Aytan N, Giannaris EL, Zeldich E, Hinman JD, Dedeoglu A, Rosene DL, Bansal R, Luebke JI, Kuro-o M, Abraham CR (2013) The antiaging protein Klotho enhances oligodendrocyte maturation and myelination of the CNS. J Neurosci 33(5):1927–1939. https://doi.org/10.1523/JNEUROSCI.2080-12.2013

Cheng KC, Inglese J (2012) A coincidence reporter-gene system for high-throughput screening; Nat Methods 9(10): 937. https://doi.org/10.1038/nmeth.2170

Cho SW, Kim S, Kim JM, Kim JS (2013) Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease. Nat Biotechnol 31(3):230–232. https://doi.org/10.1038/nbt.2507

Choi BH, Kim CG, Lim Y, Lee YH, Shin SY (2010) Transcriptional activation of the human Klotho gene by epidermal growth factor in HEK293 cells; role of Egr-1. Gene 450(1-2):121–127. https://doi.org/10.1016/j.gene.2009.11.004

Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Marraffini LA, Zhang F (2013) Multiplex genome engineering using CRISPR/Cas systems. Science 339(6121):819–823. https://doi.org/10.1126/science.1231143

Dubal DB, Yokoyama JS, Zhu L, Broestl L, Worden K, Wang D, Sturm VE, Kim D, Klein E, Yu GQ, Ho K, Eilertson KE, Yu L, Kuro-o M, de Jager PL, Coppola G, Small GW, Bennett DA, Kramer JH, Abraham CR, Miller BL, Mucke L (2014) Life extension factor klotho enhances cognition. Cell Rep 7(4):1065–1076. https://doi.org/10.1016/j.celrep.2014.03.076

Dubal DB, Zhu L, Sanchez PE, Worden K, Broestl L, Johnson E, Ho K, Yu GQ, Kim D, Betourne A, Kuro-o M, Masliah E, Abraham CR, Mucke L (2015) Life extension factor klotho prevents mortality and enhances cognition in hAPP transgenic mice. J Neurosci : Off J Socr Neuroscience 35(6):2358–2371. https://doi.org/10.1523/JNEUROSCI.5791-12.2015

Gersbach CA, Perez-Pinera P (2014) Activating human genes with zinc finger proteins, transcription activator-like effectors and CRISPR/Cas9 for gene therapy and regenerative medicine. Expert Opin Ther Targets 18(8):835–839. https://doi.org/10.1517/14728222.2014.913572

Hasson SA, Fogel AI, Wang C, MacArthur R, Guha R, Heman-Ackah S, Martin S, Youle RJ, Inglese J (2015) Chemogenomic profiling of endogenous PARK2 expression using a genome-edited coincidence reporter. ACS Chem Biol 10(5):1188–1197. https://doi.org/10.1021/cb5010417

Jinek M, East A, Cheng A, Lin S, Ma E, Doudna J (2013) RNA-programmed genome editing in human cells. elife 2:e00471

Kearns NA, Genga RM, Enuameh MS, Garber M, Wolfe SA, Maehr R (2014) Cas9 effector-mediated regulation of transcription and differentiation in human pluripotent stem cells. Development 141(1):219–223. https://doi.org/10.1242/dev.103341

King GD, Chen C, Huang MM, Zeldich E, Brazee PL, Schuman ER, Robin M, Cuny GD, Glicksman MA, Abraham CR (2012) Identification of novel small molecules that elevate Klotho expression. Biochem J 441(1):453–461. https://doi.org/10.1042/BJ20101909

Konermann S, Brigham MD, Trevino AE, Joung J, Abudayyeh OO, Barcena C, Hsu PD, Habib N, Gootenberg JS, Nishimasu H, Nureki O, Zhang F (2015) Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature 517(7536):583–588. https://doi.org/10.1038/nature14136

Kuro-o M (2012) Klotho in health and disease. Curr Opin Nephrol Hypertens 21(4):362–368. https://doi.org/10.1097/MNH.0b013e32835422ad

Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E et al (1997) Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390(6655):45–51. https://doi.org/10.1038/36285

Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P, McGuinness OP, Chikuda H, Yamaguchi M, Kawaguchi H, Shimomura I, Takayama Y, Herz J, Kahn CR, Rosenblatt KP, Kuro-o M (2005) Suppression of aging in mice by the hormone Klotho. Science 309(5742):1829–1833. https://doi.org/10.1126/science.1112766

Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, Norville JE, Church GM (2013) RNA-guided human genome engineering via Cas9. Science 339(6121):823–826. https://doi.org/10.1126/science.1232033

Massó A, Sánchez A, Bosch A, Giménez-Llort L, Chillón M (2017) Secreted αKlotho isoform protects against age-dependent memory deficits. Mol Psychiatry. https://doi.org/10.1038/mp.2017.211

Massó A, Sanchez A, Gimenez-Llort L, Lizcano JM, Canete M, Garcia B, Torres-Lista V, Puig M, Bosch A, Chillon M (2015) Secreted and transmembrane alphaKlotho isoforms have different spatio-temporal profiles in the brain during aging and Alzheimer’s disease progression. PLoS One 10(11):e0143623. https://doi.org/10.1371/journal.pone.0143623

Masuda H, Chikuda H, Suga T, Kawaguchi H, Kuro-o M (2005) Regulation of multiple ageing-like phenotypes by inducible klotho gene expression in klotho mutant mice. Mech Ageing Dev 126(12):1274–1283. https://doi.org/10.1016/j.mad.2005.07.007

Matsumura Y, Aizawa H, Shiraki-Iida T, Nagai R, Kuro-o M, Nabeshima Y (1998) Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein. Biochem Biophys Res Commun 242(3):626–630. https://doi.org/10.1006/bbrc.1997.8019

Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F (2013) Genome engineering using the CRISPR-Cas9 system. Nat Protoc 8(11):2281–2308. https://doi.org/10.1038/nprot.2013.143

Schuck BW, MacArthur R, Inglese J (2017) Quantitative high-throughput screening using a coincidence reporter biocircuit. Curr Protoc Neurosci 79:5 32 31–35 32 27

Zeldich E, Chen CD, Avila R, Medicetty S, Abraham CR (2015) The anti-aging protein Klotho enhances remyelination following cuprizone-induced demyelination. J Mol Neurosci : MN 57(2):185–196. https://doi.org/10.1007/s12031-015-0598-2

Zeldich E, Chen CD, Colvin TA, Bove-Fenderson EA, Liang J, Tucker Zhou TB, Harris DA, Abraham CR (2014) The neuroprotective effect of klotho is mediated via regulation of members of the redox system. J Biol Chem 289(35):24700–24715. https://doi.org/10.1074/jbc.M114.567321