(AD) β (A ) (2) ACDP ACDP ACDP APP. APP-C99 γ (3) A 40 A 42 A A A A 42/A 40. in vivo A A A A

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2 (AD) β (A) A AAPP APP-C99 γ A A40 A42 A AA42/A40 γ A A γ AD A A A A APP APP APP A A A A A A (1)AD A42 A AD AD (2) ACDP AACDP ACDP A A ACDP (3) (1)A in vivo A APP Gray and Whittaker 1962; Perez-Otano et al. 2006; Phillips 2001 Lassek et al (2) γ A42 A(J Neurochem 123:21-28, 2012) γ Presenilin Presenilin A42 AD Presenilin A AD A (60 ) A42 AD ( 15 ) Presenilin -1 γ AD

Presenilin-1 Ser/Thr Tyr Lys SUMO ADP Tyr (3)AACDP AD ACDP APP-C99 A AD ACDP A ACDP ACDP A AACDP ACDP ILEI ACDP (Luc) ACDP Aβ (1)Aβ APP J Neurochem 133:422-431, 2015 (2) Aβ42 Presenilin-1 HEK293

3 Presenilin-1 Ser/Thr Tyr Lys SUMO ADP Tyr (3)AACDP AD ACDP APP-C99 A AD ACDP A ACDP ACDP A AACDP ACDP ILEI ACDP (Luc) ACDP Aβ (1)Aβ APP J Neurochem 133: , 2015 (2) Aβ42 Presenilin-1 HEK293 Presenilin-1 Ser/Thr Tyr Lys Tyr (3)Aβ ILEI (ACDP) AD ACDP ILEI (Nat Commun 5:3917, 2014)ACDP ILEI ILEI A Nat Commun 5:3917, 2014; Neuroscience 330: , 2016) ILEI A ILEI A ILEI Neuroscience 330: , 2016) HEK kb kb kb SH-SY5Y HEK293 ILEI Aβ ILEI APP-C99 Aβ Presenilin-1 C DQL

3D-RISM Aβ ILEI DQL ILEI Lys84 Lys84 ILEI HEK293 12 γ ILEI/FAM3C β β ILEI/FAM3C 17(2): 14-20, 2017 Liu L, Watanabe N, Akatsu H, Nishimura M.

4 3D-RISM Aβ ILEI DQL ILEI Lys84 Lys84 ILEI HEK γ ILEI/FAM3C β β ILEI/FAM3C 17(2): 14-20, 2017 Liu L, Watanabe N, Akatsu H, Nishimura M. Neuronal expression of ILEI/FAM3C and its reduction in Alzheimer's disease. Neuroscience 330: , 2016 doi: /j.neuroscience Seita Y, Tsukiyama T, Iwatani C, Tsuchiya H, Matsushita J, Azami T, Okahara J, Nakamura S, Hayashi Y, Hitoshi S, Itoh Y, Imamura T, Nishimura M, Tooyama I, Miyoshi H, Saitou M, Ogasawara K, Sasaki E, Ema M. Generation of transgenic cynomolgus monkeys that express green fluorescent protein throughout the whole body. Sci Rep 6:24868, 2016 doi: /srep Ochiishi T, Itakura A, Liu L, Akatsu H, Kohno H, Nishimura M, Yoshimune K. Immunohistochemical detection of the delayed formation of non-fibrillar large amyloid- aggregates. Genes Cells 21: , 2016 doi: /gtc Abdelalim EM, Bellier JP, Tooyama I. Localization of brain natriuretic peptide immunoreactivity in rat spinal cord. Front Neuroanat 10:116, ecollection 2016 Wang X, Yang H, Yanagisawa D, Bellier JP, Morino K, Zhao S, Liu P, Vigers P, Tooyama I. Mitochondrial ferritin affects mitochondria by stabilizing HIF-1α in retinal pigment epithelium: implications for the pathophysiology of age-related macular degeneration. Neurobiol Aging 47: , 2016 doi: /j.neurobiolaging Yang M, Yang H, Guan H, Bellier JP, Zhao S, Tooyama I. Mapping of mitochondrial ferritin in the brainstem of Macaca fascicularis. Neuroscience 328:92-106, 2016 doi: /j.neuroscience (1): 29-34, 2016 Liu L, Fujino K, Nishimura M. Presynaptic localization of the -secretase-inhibiting protein p24 2 in the mammalian brain. J Neurochem 133: , 2015 doi: /jnc Hasegawa H, Liu L, Tooyama I, Murayama S, Nishimura M. The FAM3 superfamily member ILEI ameliorates Alzheimer's disease-like pathology by destabilizing the penultimate amyloid- precursor. Nat Commun 5:3917, 2014 doi: /ncomms4917. Han J, Jung S, Jang J, Kam TI, Choi H, Kim BJ, Nah J, Jo DG, Nakagawa T, Nishimura M, Jung YK. OCIAD2 activates γ-secretase to enhance amyloid β production by interacting with nicastrin. Cell Mol Life Sci 71(13): , 2014 doi: /s x. 15 Nishimura MILEI in the pathogenesis of Alzheimer s disease. International Symposium Alzheimer s disease: Narrowing the gap between basic science and clinical application Niigata University, March 10-11, 2017 Nishimura M, Liu L, Watanabe N, Akatsu H. Neuronal expression of ILEI/FAM3C and its reduction in Alzheimer's disease. Alzheimer s Association International Conference 2016, Toronto, July 2016 γ

5 γ Watanabe NLiu LNishimura M. Brain distribution and subcellular localization of ILEI/FAM3C and its reduction with aging. 39, ,,,,. AmyloidILEI/FAM3C ,,, A ILEI/FAM3C Nishimura M, Liu L, Tooyama I. Neuronal ILEI reduces amyloid- production by destabilizing amyloid precursor protein. The 12th International Conference on Alzheimer's & Parkison's Diseases, March 18-22, 2015, Nice Liu L, Nishimura M. Aβ generation is regulated by p24α2 at the presynaptic terminals. BMB2015, December 1-4, 2015, Kobe Liu L, Nishimura M. Pre-synaptic localization of p24α2 in the mammalian brain Aβ ILEI Nishimura M, Liu L, Fujino K. p242 interacts with -secretase complex at presynaptic terminals. Alzheimer s Association International Conference 2014, July 12-17, 2014, Copenhagen Nishimura M, Liu L. Expression of p242 in mammalian brain. Experimental Biology 2014, April 26-30, 2014, San Diego. ILEI Liu L, Hiroshi Hasegawa H, Tooyama I, Murayama S, Nishimura M. ILEI reduces amyloid- generation by destabilizing APP-C Q & A Neo, 2016, p , 2014, NISHIMURA, Masaki

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