Carboxyl-terminal fragments of presenilin-1 are closely related to cytoskeletal abnormalities in Alzheimer's brains

被引：11

作者：

Tomidokoro, Y

Ishiguro, K

Igeta, Y

Matsubara, E

Kanai, M

Shizuka, M

Kawarabayashi, T

Harigaya, Y

Kawakatsu, S

Ii, K

Ikeda, M

George-Hyslop, PHS

Hirai, S

Okamoto, K

Shoji, M

机构：

[1] Gunma Univ, Sch Med, Dept Neurol, Gunma 3718511, Japan

[2] Yamagata Univ, Fac Med, Dept Psychiat, Yamagata 9902331, Japan

[3] Univ Tokushima, Sch Med, Dept Pathol 1, Tokushima 7708503, Japan

[4] Univ Toronto, Dept Med Neurol, Ctr Res Neurodegenerat Dis, Toronto, ON, Canada

[5] Toronto Hosp, Dept Med, Div Neurol, Toronto, ON M5S 1A8, Canada

[6] Tokyo Metropolitan Neurol Hosp, Tokyo 1830042, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1999年 / 256卷 / 03期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1006/bbrc.1998.0119

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

To clarify the role of presenilin-1 (PS-1) in the pathology of Alzheimer's disease (AD), we tested four antisera to PS-1. The specific antisera to the N-terminus (HSN-2) and C-terminus (HS-C) of PS-1 detected a 44/40kD holo-protein, a 25kD N-terminal fragment (NTF) and a 16kD C-terminal fragment (CTF) of PS-1 in COS-7 cells. The 25kD NTF and 16kD CTF were observed in human brains, and their amounts were not significantly different between the control and AD brains. The antibody HS-C labeled extensive neurofibrillary tangles, dystrophic neurites and curly fibers in the AD brains, In the paired helical filament (PHF) fraction containing A68 protein-from AD brains, a smear pattern of CTFs was revealed. Antisera (HS-L292 and HS-L300) to cleavage sites of PS-1 also revealed immunoreactive neurofibrillary tangles in the AD brain sections and the: smear pattern of CTFs of A68 protein fraction. The CTFs of PS-1 accumulate with PHF tau, suggesting a close relationship between PS-1 and cytoskeletal abnormalities in AD brains. (C) 1999 Academic Press.

引用

页码：512 / 518

页数：7

共 29 条

[1] Neuronal localization of presenilin-1 and association with amyloid plaques and neurofibrillary tangles in Alzheimer's disease [J].

Busciglio, J ;

Hartmann, H ;

Lorenzo, A ;

Wong, C ;

Baumann, K ;

Sommer, B ;

Staufenbiel, M ;

Yankner, BA .

JOURNAL OF NEUROSCIENCE, 1997, 17 (13) :5101-5107

[2] Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice [J].

Citron, M ;

Westaway, D ;

Xia, WM ;

Carlson, G ;

Diehl, T ;

Levesque, G ;

JohnsonWood, K ;

Lee, M ;

Seubert, P ;

Davis, A ;

Kholodenko, D ;

Motter, R ;

Sherrington, R ;

Perry, B ;

Yao, H ;

Strome, R ;

Lieberburg, I ;

Rommens, J ;

Kim, S ;

Schenk, D ;

Fraser, P ;

Hyslop, PS ;

Selkoe, DJ .

NATURE MEDICINE, 1997, 3 (01) :67-72

[3] Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein [J].

De Strooper, B ;

Saftig, P ;

Craessaerts, K ;

Vanderstichele, H ;

Guhde, G ;

Annaert, W ;

Von Figura, K ;

Van Leuven, F .

NATURE, 1998, 391 (6665) :387-390

[4] Protein topology of presenilin 1 [J].

Doan, A ;

Thinakaran, G ;

Borchelt, DR ;

Slunt, HH ;

Ratovitsky, T ;

Podlisny, M ;

Selkoe, DJ ;

Seeger, M ;

Gandy, SE ;

Price, DL ;

Sisodia, SS .

NEURON, 1996, 17 (05) :1023-1030

[5] MODIFIED AMYLOID-BETA PROTEIN ENDING AT 42 OR 40 WITH DIFFERENT SOLUBILITY ACCUMULATES IN THE BRAIN OF ALZHEIMERS-DISEASE [J].

HARIGAYA, Y ;

SHOJI, M ;

KAWARABAYASHI, T ;

KANAI, M ;

NAKAMURA, T ;

IIZUKA, T ;

IGETA, Y ;

SAIDO, TC ;

SAHARA, N ;

MORI, H ;

HIRAI, S .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1995, 211 (03) :1015-1022

[6] The clinical phenotype of two missense mutations in the presenilin I gene in Japanese patients [J].

Ikeda, M ;

Sharma, V ;

Sumi, M ;

Rogaeva, EA ;

Poorkaj, P ;

Sherrington, R ;

Nee, L ;

Tsuda, T ;

Oda, N ;

Watanabe, M ;

Aoki, M ;

Shoji, M ;

Abe, K ;

Itoyama, Y ;

Hirai, S ;

Schellenberg, GD ;

Bird, TD ;

StGeorgeHyslop, PH .

ANNALS OF NEUROLOGY, 1996, 40 (06) :912-917

[7] Increased A beta 42(43)-plaque deposition in early-onset familial Alzheimer's disease brains with the deletion of exon 9 and the missense point mutation (H163R) in the PS-1 gene [J].

Ishii, K ;

Ii, K ;

Hasegawa, T ;

Shoji, S ;

Doi, A ;

Mori, H .

NEUROSCIENCE LETTERS, 1997, 228 (01) :17-20

[8] Three different mutations of presenilin 1 gene in early-onset Alzheimer's disease families [J].

Kamino, K ;

Sato, S ;

Sakaki, Y ;

Yoshiiwa, A ;

Nishiwaki, Y ;

Takeda, M ;

Tanabe, H ;

Nishimura, T ;

Ii, K ;

StGeorgeHyslop, PH ;

Miki, T ;

Ogihara, T .

NEUROSCIENCE LETTERS, 1996, 208 (03) :195-198

[9] Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease [J].

Kim, TW ;

Pettingell, WH ;

Jung, YK ;

Kovacs, DM ;

Tanzi, RE .

SCIENCE, 1997, 277 (5324) :373-376

[10] Alzheimer-associated presenilins 1 and 2: Neuronal expression in brain and localization to intracellular membranes in mammalian cells [J].

Kovacs, DM ;

Fausett, HJ ;

Page, KJ ;

Kim, TW ;

Moir, RD ;

Merriam, DE ;

Hollister, RD ;

Hallmark, OG ;

Mancini, R ;

Felsenstein, KM ;

Hyman, BT ;

Tanzi, RE ;

Wasco, W .

NATURE MEDICINE, 1996, 2 (02) :224-229

← 1 2 3 →