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Photo Molecular Neuroscience Laboratory
Mechanisms that maintain the functional and structural integrity of neurons and their disruption in aging and disease

Our brains enable us to laugh, dance, love, and create. Brains are made up of networks of neuronal cells, which process and store huge amount of information. The vast majority of neurons that operate your brain last a lifetime and are not replaced and loss of neurons causes neurodegenerative diseases such as Alzheimerüfs disease. How can we keep our brain functions during aging and reduce the risk of age-associated neurodegenerative diseases?

We tackle these questions with focuses on mitochondrial distribution in neurons and microtubule-binding protein tau, both of which play key roles in the pathogenesis of Alzheimerüfs disease and other neurodegenerative diseases.
Our current research projects include (1) How tau gain toxicity in disease pathogenesis, (2) mechanisms underlying depletion of axonal mitochondria increase neuronal vulnerability, (3) age-dependent changes in local energy metabolism in neurons and risks of neurodegenerative diseases.
As experimental approaches, we use Drosophila models, molecular biology, biochemistry, behavioral analysis, gene expression analysis, and imaging.

We hope discoveries from this research enhance understanding of disease pathogenesis and contribute to increasing our healthspan.

As for Kanae Andoüfs publication before 2014, please see:
https://www.researchgate.net/profile/Kanae_Ando
Faculty
Asc Prof Kanae Ando e-mail
Ast Prof Akiko Asada e-mail
Ast Prof Taro Saito e-mail
How microtubule associated protein tau gain toxicity in disease pathogenesis
Coming soon
Mechanisms underlying depletion of axonal mitochondria increase neuronal vulnerability
Coming soon
Age-dependent changes in local energy metabolism in neurons and risks of neurodegenerative diseases.
Coming soon
Recent Publications
  1. Sekiya M, Wang M, Fujisaki N, Sakakibara Y, Quan X, Ehrlich ME, De Jager PL, Bennett DA, Schadt EE, Gandy S, Ando K, Zhang B, Iijima KM.Genome Med. 2018 Mar 29;10(1):26. doi: 10.1186/s13073-018-0530-9.Integrated biology approach reveals molecular and pathological interactions among Alzheimer's Aâ└42, Tau, TREM2, and TYROBP in Drosophila models.
  2. Kimura, T., Sharma, G., Ishiguro, K., Hisanaga, S. Phospho-tau bar code: analysis of phosphoisotypes of tau and its application to tauopathy. Fron. Mol. Neurosci., 12, 44, 2018.
  3. Tuerde, D., Kimura, T., Miyasaka, T., Furusawa, K., Shimozawa, A., Hasegawa, M., Ando, K., Hisanaga, SI. Isoform-independent and -dependent phosphorylation of microtubule-associated protein tau in mouse brain during postnatal development. J. Biol. Chem. 293: 1781-1793, 2018
  4. Furusawa, K., Asada, A., Urrutia, P., Gonzalez-Billault, C., Fukuda, M., Hisanaga, SI. Cdk5 Regulation of the GRAB-Mediated Rab8-Rab11 Cascade in Axon Outgrowth. J Neurosci. 37: 790-806., 2017.
  5. Akasaka-Manya, K., Kawamura, M., Tsumoto, H., Saitoh, Y., Shinobu Kitazume, S., Hatsuda, H., Miura, Y., Hisanaga, S., Murayama, S., Hashimoto, Y., Manya, H., Endo, T. Excess APP O-glycosylation by GalNAc-T6 decreases Aâ└ production. J. Biochem. 161:99-111, 2017
  6. Krishnankutty, A., Kimura, T., Saito, T., Aoyagi, K., Asada, A., Takahashi, S., Ando, K., Ohara-Imaizumi, M., Ishiguro, K., Hisanaga, S. In vivo regulation of glycogen synthase kinase 3â└ activity in neurons and brains. Sci. Rep. Sci. Rep. 7, 8602, 2017.
  7. Sekiya, M., Maruko-Otake, A., Hearn, S., Sakakibara, Y., Fujisaki, N., Suzuki, E., Ando, K., Iijima, K. M.
  8. EDEM Function in ERAD Protects against Chronic ER Proteinopathy and Age-Related Physiological Decline in Drosophila. Dev Cell. 2017 Jun 19;41(6):652-664.e5. doi: 10.1016/j.devcel.2017.05.019.
  9. Oka, M., Iijima, K.M. and Ando, K.* (2017) Loss of synaptic mitochondria and dementia. Zikkennigaku, Yodosha (Japanese) Vol35, No12, p182-185, Yodosha
  10. Ando, K.*, Hearn, A., Suzuki, E., Maruko-Otake, A., Sekiya, M., and Iijima, K.M. (2015) Electron microscopy of the brains of Drosophila Models of Alzheimerüfs disease. Neuromethods, DOI 10.1007/7657_2015_75, Springer
  11. Kimura, T., Hosokawa, T., Taoka, T., Tsutsumi, T., Ando, K., Ishiguro, K., Hosokawa, M., Hasegawa, M. and Hisanaga, S. (2016) Quantitative and combinatory determination of in situ phosphorylation of tau and its FTDP-17 mutants. Scientific Reports, ep 19;6:33479. doi: 10.1038/srep33479.
  12. Sharma, G., Tsutsumi, T., Saito, T., Asada, A., Ando, K., Tomomura, M., and Hisanaga, S. The kinase activity of endosomal kinase LMTK1A regulates its cellular localization and interactions with cytoskeletons. Genes to Cells, 2016 Oct;21(10):1080-1094. doi: 10.1111/gtc.12404.
  13. Ando, K*, Oka, M., Ohtake, Y., Hayashishita, M., Shimizu, S., Hisanaga, S., and Iijima, K.M.* (2016) Tau phosphorylation at Alzheimer's disease-related Ser356 contributes to tau stabilization when PAR-1/MARK activity is elevated. Biochemical and Biophysical Research Communications, Volume 478, Issue 2, Pages 929–934
  14. Ando, K.*, Maruko-Otake, A., Ohtake, Y., Hayashishita, M., Sekiya, M., and Iijima, K. M. (2016) Stabilization of microtubule-unbound tau via tau phosphorylation at Ser262/356 by Par-1/MARK contributes to augmentation of AD-related phosphorylation and Aâ└42-induced tau toxicity. PLoS Genetics (12(3): e1005917. doi:10.1371/journal. pgen.1005917)
  15. Zhu, Y-S., Saito, T., Asada, A., Maekawa, S., and Hisanaga, S. Activation of latent cyclin-dependent kinase 5 (Cdk5)?p35 complexes by membrane dissociation. J. Neurochem. In press. (2005)
  16. Ohshima, T., Ogura, H., Tomizawa, K., Hayashi, K., Suzuki, H., Saito, T., Kamei, H., Nishi, A., Bibb, J. A., Hisanaga, S., Matsui, H., and Mikoshiba, K. Impairment of Hippocampal Long-Term Depression and Defective Spatial Learning and Memory in p35-/- Mice. J. Neurochem. In press.ü@
  17. Taniguchi, S., Suzuki, N., Masuda, M., Hisanaga, S., Iwatsubo, T., Goedert, M., and Hasegawa, M. Inhibition of heparin-induced tau filament formation by phenotiazine, polyphenols and porphyrins. J. Biol. Chem. 280, 7614-7623, 2005.
  18. Permana, S., Hisanaga, S., Nagatomo, Y., Iida, J., Hotani, H., and Itoh, T. J. Truncation of the projection domain of MAP4 (Microtubule-associated protein 4) leads to the attenuation of dynamic instability of microtubules. Cell Str. Funct. 29, 147-157, 2005.
  19. Wei, F-Y., Tomizawa, K., Ohshima, T., Asada, A., Saito, T., Nguyen, C., Bibb, J. A., Ishiguro, K., Kulkarni, A. B., Pant, H. C., Mikoshiba, K., Matsui, H., and Hisanaga. S. Control of Cyclin-dependent kinase 5 (Cdk5) activity by glutamatergic regulation of p35 stability. J. Neurochem. 93, 502-512, 2005.
  20. Hatanaka, Y., Hisanaga, S., Heizmann, C. W., and Murakami, F. Distinct migratory ehavior of early-and late-born neurons in the cerebral cortex. J. Comp. Neurol. 479, 1-14, 2004.
  21. Alim, M. A., Ma, Q-L., Takeda, K., Aizawa, T., Matsubara, M., Nakamura, M., Saito, T., Asada, A., Kaji, H., Yoshii, M., Hisanaga, S., and
  22. Ueda, K. Demonstration of a role for alpha-synuclein as a functional microtubule-associated protein. J. Alz. Dis. 6: 435-442, 2004.
  23. Uchida, A., Tashiro, T., Komiya, Y., Yorifuji, H., Kishimoto, T., and Hisanaga, S. Morphological and biochemical changes of neurofilaments in aged rat sciatic nerve axons. J. Neurochem. 88: 735-745, 2004.
  24. Hisanaga, S., and Saito, T. The regulation of Cdk5 kinase activity through the metabolism of p35 or p39 Cdk5 activator . Neurosignals 12: 221-229, 2004.
  25. Tomizawa, K., Sunada, S., Lu, Y-F., Oda, Y., Kinuta, M., Ohshima, T., Saito, T., Matsushita, M., Li, S-T., Moriwaki, A., Tsutsui, K.,
  26. Hisanaga, S., Mikoshiba, K., Takei, K., and Matsui, H. Cdk5/p35-dependent Phosphorylation of Amphiphysin I and Dynamin I: Critical Role in Clathrin-mediated Endocytosis of Synaptic Vesicles. J. Cell Biol., 163: 813-824, 2003.
  27. Honma, N., Asada, A., Takeshita, S., Enomoto, M., Yamakawa, E., Tsutsumi, K., Saito, T., Satoh, T., Itoh, H., Kaziro, Y., Kishimoto, T., and Hisanaga, S. Apoptosis-associated tyrosine kinase (AATYK) is a Cdk5 activator p35 binding protein. Biochem. Biophys. Res. Commun. 310: 398-404, 2003.
  28. Kawachi, A., Ichihara, K., Hisanaga, S., Iida, J., Toyota, H., Hotani, H., and Itoh, T. J. Different protofilament-dependence of the microtubule binding between MAP2 and MAP4. Biochem. Biophys. Res. Commun., 305: 72-78, 2003.
  29. Takahashi, S., Saito, T., Hisanaga, S., Pant, H. C., and Kulkarni, A.B. Tau phosphorylation by cyclin-dependent kinase 5/p39 during brain development reduces its affinity for microtubules. J. Biol. Chem. 278: 10506-10515, 2003.
  30. Saito, T., Onuki, R., Fujita, Y., Kusakawa, G., Ishiguro, K., Bibb, J.A., Kishimoto, T., and Hisanaga, S. Developmental regulation of the proteolysis of the p35 Cdk5 activator by phosphorylation. J. Neurosci, 23: 1189-1197, 2003.
  31. Hashiguchi, M., Saito,T., Hisanaga, S., and Hashiguchi, T. Truncation of CDK5 activator p35 induces intensive phosphorylation of Ser202/Thr205 of human tau 40. J. Biol.Chem. 277: 44524-44530, 2002.
  32. Sasaki, T., Taoka, M., Ishiguro,K., Uchida,A., Saito,T., Isobe, T., and Hisanaga,S. In [1] <#_msocom_1> vivo and in vitro phosphorylation at Ser493 in the E-segment of neurofilament-H subunit by GSK3b. J. Biol. Chem. 277:36032-36039, 2002.
  33. Iida, J., Itoh, T. J., Hotani, H., Nishiyama, K., Murofushi, H., Bulinski, J. C., and Hisanaga, S. The projection domain of MAP4 suppresses the microtubule-bundling activity of the microtubule-binding domain. J. Mol. Biol. 320: 97-106, 2002.
  34. Alim, M.A., Hossain, M. S., Arima, K., Takeda, K., Izumiyama, Y., Nakamura, M., Kaji, H., Shinoda, T., Hisanaga, S., and Ueda, K. Tubulin seeds a-synuclein fibril formation. J. Biol. Chem. 272:2112-2117,2002.
©2015 Department of Biological Sciences, Tokyo Metropolitan University