Abstract
▪ Abstract Intensive studies of three proteins—Presenilin, Notch, and the amyloid precursor protein (APP)—have led to the recognition of a direct intersection between early development and late-life neurodegeneration. Notch signaling mediates many different intercellular communication events that are essential for determining the fates of neural and nonneural cells during development and in the adult. The Notch receptor acts in a core pathway as a membrane-bound transcription factor that is released to the nucleus by a two-step cleavage mechanism called regulated intramembrane proteolysis (RIP). The second cleavage is effected by Presenilin, an unusual polytopic aspartyl protease that apparently cleaves Notch and numerous other single-transmembrane substrates within the lipid bilayer. Another Presenilin substrate, APP, releases the amyloid ß-protein that can accumulate over time in limbic and association cortices and help initiate Alzheimer's disease. Elucidating the detailed mechanism of Presenilin processing of membrane proteins is important for understanding diverse signal transduction pathways and potentially for treating and preventing Alzheimer's disease.
References
248
Referenced
521
10.1186/1471-213X-1-13
10.1016/S0959-437X(02)00336-2
10.1016/0168-9525(91)90220-K
10.1002/(SICI)1521-1878(200003)22:3<264::AID-BIES8>3.3.CO;2-D
10.1101/gad.987402
10.1016/S0092-8674(00)00198-7
10.1002/(SICI)1097-4547(19981015)54:2<125::AID-JNR1>3.3.CO;2-C
10.1016/S1534-5807(02)00215-0
10.1016/S0169-328X(99)00119-9
10.1046/j.1471-4159.2000.0750583.x
10.1074/jbc.M008268200
10.1016/S0306-4522(99)00157-8
10.1016/S0960-9822(00)00633-3
10.1016/S0092-8674(00)80336-0
10.1016/S0896-6273(00)80230-5
10.1016/S0092-8674(00)81180-0
10.1016/S0960-9822(99)80313-3
10.1093/genetics/147.1.177
/ Genetics by Brennan K (1997)10.1006/dbio.1999.9501
10.1016/S1097-2765(00)80417-7
10.1016/S0092-8674(00)80675-3
10.1038/35019075
10.1006/dbio.2000.9992
10.1038/2673
10.1007/BF02740668
10.1016/S0896-6273(00)80274-3
10.1074/jbc.273.6.3205
10.1242/dev.128.5.689
/ Development by Chambers CB (2001)10.1016/S0959-4388(99)00017-3
10.1074/jbc.M205093200
10.1016/S0959-437X(02)00326-X
10.1038/375761a0
10.1038/ncb1201-1129
10.1038/nm0197-67
10.1242/dev.121.5.1533
/ Development by Conlon RA (1995)10.1093/genetics/152.2.567
/ Genetics by Cornell M (1999)10.1242/dev.120.10.2901
/ Development by Crittenden SL (1994)10.1046/j.1471-4159.2001.00516.x
10.1016/S1534-5807(01)00091-0
10.1242/dev.124.6.1139
/ Development by de la Pompa JL (1997)10.1038/19083
10.1038/34910
10.1101/gad.13.21.2801
10.1038/383710a0
10.1074/jbc.M111571200
10.1073/pnas.97.22.11692
10.1016/S0092-8674(00)80561-9
10.1038/35017062
10.1073/pnas.052436599
10.1021/bi00043a024
10.1016/S0959-4388(02)00287-8
10.1006/nbdi.2001.0447
10.4049/jimmunol.169.4.1817
10.1016/S1534-5807(02)00189-2
10.1016/S0960-9822(00)80114-1
10.1101/gad.991602
10.1146/annurev.neuro.25.030702.130823
10.1016/S0896-6273(00)81172-1
10.1016/S1097-2765(00)80219-1
10.1242/dev.126.16.3573
/ Development by Gho M (1999)10.1016/S0896-6273(00)81007-7
10.1242/dev.117.2.431
/ Development by Giniger E (1993)10.1242/dev.127.11.2481
/ Development by Goutte C (2000)10.1073/pnas.022523499
10.1006/mcne.1997.0610
10.1074/jbc.C100357200
10.1074/jbc.M101343200
10.1126/science.286.5441.916
10.1242/dev.125.23.4637
/ Development by Haddon C (1998)10.1242/dev.125.3.359
/ Development by Haddon C (1998)10.1242/dev.126.15.3415
/ Development by Hamada Y (1999)10.1242/dev.127.12.2593
/ Development by Handler M (2000)10.1093/hmg/11.21.2615
10.1016/0092-8674(91)90263-X
10.1242/dev.117.3.1113
/ Development by Heitzler P (1993)10.1073/pnas.96.21.11872
10.1038/35017105
10.1038/35019553
10.1002/jnr.10263
10.1101/gad.975202
10.1016/S1534-5807(01)00105-8
10.1016/S0959-437X(00)00231-8
10.1093/genetics/145.2.359
/ Genetics by Hukriede NA (1997)10.1242/dev.124.17.3427
/ Development by Hukriede NA (1997)10.1038/35016111
10.1128/MCB.21.12.3888-3900.2001
10.1016/S0959-437X(99)80066-5
10.1016/0896-6273(94)90458-8
10.1242/dev.125.22.4531
/ Development by Jacobsen TL (1998)10.1021/bi00069a001
10.1016/S0959-4388(00)00136-7
10.1083/jcb.200201123
10.1016/S1357-2725(97)89968-2
-
Kamal A, Almenar-Queralt A, LeBlanc JF, Roberts EA, Goldstein LS. 2001. Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. Nature414:643–48
(
10.1038/414643a
) 10.1046/j.1432-0436.2001.680208.x
10.1016/S0092-8674(02)00970-4
10.1016/S0925-4773(02)00120-X
10.1074/jbc.M210179200
10.1074/jbc.272.17.11006
10.1073/pnas.1037392100
10.1074/jbc.M204446200
10.1074/jbc.275.5.3173
10.1074/jbc.C100447200
10.1146/annurev.cellbio.13.1.333
10.1146/annurev.ne.15.030192.001343
10.1242/jcs.112.19.3289
/ J. Cell Sci. by Klueg KM (1999)10.1016/S0955-0674(97)80085-3
10.1242/jcs.115.6.1095
/ J. Cell Sci. by Kopan R (2002)10.1016/S0959-4388(96)80090-0
10.1006/mcne.1999.0783
10.1016/S1534-5807(01)00095-8
10.1101/gad.14.11.1343
/ Genes Dev. by Krebs LT (2000)10.1016/S0378-1119(96)00673-7
10.1016/S0021-9258(17)32325-6
/ J. Biol. Chem. by Ladror US (1994)10.1016/S1534-5807(01)00092-2
10.1074/jbc.M206872200
{'key': 'b117', 'first-page': 'S176', 'volume': '23', 'author': 'LaVoie M', 'year': '2002', 'journal-title': 'Neurobiol. Aging'}
/ Neurobiol. Aging by LaVoie M (2002)10.1074/jbc.M110371200
10.1074/jbc.C200148200
10.1038/nm1096-1146
10.1038/377351a0
10.1006/dbio.2001.0486
10.1159/000064948
10.1126/science.7638622
10.1016/S0959-4388(96)80002-X
10.1006/scdb.1998.0266
10.1073/pnas.95.12.7109
10.1038/35015085
10.1073/pnas.032395699
10.1073/pnas.96.6.3053
10.1101/gad.942302
10.1038/35053522
10.1073/pnas.95.14.8108
10.1016/S1534-5807(01)00109-5
10.1016/S0166-2236(00)01888-9
10.1093/emboj/21.8.1948
10.1074/jbc.M201979200
10.1242/dev.124.8.1485
/ Development by Micchelli CA (1997)10.1074/jbc.M110023200
{'key': 'b140', 'first-page': 'S209', 'volume': '23', 'author': 'Moehlmann T', 'year': '2002', 'journal-title': 'Neurobiol. Aging'}
/ Neurobiol. Aging by Moehlmann T (2002)10.1073/pnas.112686799
10.1038/35019000
10.1016/S0960-9822(01)00224-X
10.1016/S0955-0674(00)00269-6
10.1006/dbio.2000.9960
10.1016/S1097-2765(00)80416-5
10.1016/S0960-9822(00)00578-9
10.1016/S0896-6273(00)80637-6
10.1002/jcb.1110
10.1126/science.1065412
10.1016/S0896-6273(01)00214-8
10.1074/jbc.M103992200
10.1242/dev.121.10.3291
/ Development by Oka C (1995)10.1038/35075094
-
Okajima T, Irvine KD. 2002. Regulation of notch signaling by o-linked fucose. Cell111:893–904
(
10.1016/S0092-8674(02)01114-5
) 10.1093/emboj/cdf541
10.1093/emboj/cdf549
10.1016/S0092-8674(00)80335-9
10.1006/scdb.1998.0263
10.1074/jbc.M204445200
10.1242/dev.127.7.1373
/ Development by Parks AL (2000)10.1016/S1534-5807(01)00093-4
10.1007/PL00000685
10.1126/science.282.5392.1281
10.1006/nbdi.1997.0129
10.1093/hmg/11.9.1037
10.1016/0092-8674(94)90105-8
10.1097/00001756-200110290-00035
10.1126/science.283.5398.91
10.1016/S0896-6273(00)80999-X
10.1016/S0960-9822(01)00562-0
10.1074/jbc.272.39.24536
10.1016/S1097-2765(00)80006-4
10.1074/jbc.274.51.36801
10.1073/pnas.96.6.3263
10.1038/71104
10.1038/376775a0
10.1006/dbio.1999.9483
10.1083/jcb.151.6.1345
10.1093/embo-reports/kve180
10.1074/jbc.M909624199
10.1038/nm0896-864
10.1002/(SICI)1096-9861(20000306)418:2<121::AID-CNE1>3.3.CO;2-D
10.1038/30756
10.1038/30756
10.1073/pnas.94.10.5090
10.1146/annurev.cb.10.110194.002105
10.1126/science.286.5440.741
10.1006/dbio.1997.8723
10.1016/S0092-8674(00)80244-5
10.1038/375754a0
10.1074/jbc.M103473200
10.1016/S0959-437X(97)80083-4
10.1006/scdb.1998.0265
10.1038/nrn785
10.1073/pnas.92.14.6592
10.1083/jcb.152.4.785
10.1242/dev.124.23.4769
/ Development by Sotillos S (1997)10.1074/jbc.273.48.32322
10.1074/jbc.274.40.28669
10.1038/35041097
10.1016/S0959-437X(02)00324-6
10.1016/S1097-2765(00)00061-7
10.1038/19091
10.1242/dev.122.8.2465
/ Development by Sun X (1996)10.1242/dev.124.17.3439
/ Development by Sun X (1997)10.1016/S0092-8674(01)00224-0
10.1101/gad.8.6.707
10.1128/MCB.18.1.644
10.1016/S0896-6273(00)80291-3
10.1074/jbc.272.45.28415
10.1093/emboj/19.20.5460
10.1016/S0014-5793(02)02802-8
10.1073/pnas.94.5.2025
10.1242/dev.126.24.5725
/ Development by Tomlinson A (1999)10.1016/S0014-5793(01)03278-1
10.1016/S0959-437X(02)00327-1
10.1242/jcs.113.23.4313
/ J. Cell Sci. by Varnum-Finney B (2000)10.1002/dvdy.1145
10.1016/S0896-6273(00)00028-3
10.1242/dev.124.22.4435
/ Development by Wang S (1997)10.1021/bi015794o
10.1038/nm0397-328
10.1126/science.1070925
10.1242/dev.124.23.4759
/ Development by Wen C (1997)10.1074/jbc.275.13.9099
10.1242/dev.124.3.693
/ Development by Wettstein DA (1997)10.1038/35018575
10.1021/jm970621b
10.1021/bi991080q
10.1126/science.1073844
10.1038/19077
10.1038/387288a0
10.1128/MCB.21.21.7403-7415.2001
10.1016/S0959-4388(99)00020-3
10.1073/pnas.94.15.8208
-
Xia X, Wang P, Sun X, Soriano S, Shum W-K, et al. 2002. The aspartate-257 of Presenilin-1 is indispensable for mouse development and production of ß-amyloid peptides through ß-catenin-independent mechanisms. Proc. Natl. Acad. Sci. USA99:8760–65
(
10.1073/pnas.132045399
) 10.1074/jbc.274.46.32543
10.1074/jbc.M110871200
10.1038/19096
10.1016/S0960-9822(01)00527-9
10.1074/jbc.C100410200
10.1074/jbc.273.26.16470
10.1038/35024009
10.1101/gad.12.8.1086
10.1074/jbc.M105375200
10.1038/35017108
10.1128/MCB.21.18.6222-6232.2001
Dates
Type | When |
---|---|
Created | 22 years, 4 months ago (April 21, 2003, 8:15 p.m.) |
Deposited | 2 years, 3 months ago (April 26, 2023, 1:06 a.m.) |
Indexed | 3 weeks, 1 day ago (July 30, 2025, 8:23 p.m.) |
Issued | 22 years, 5 months ago (March 1, 2003) |
Published | 22 years, 5 months ago (March 1, 2003) |
Published Print | 22 years, 5 months ago (March 1, 2003) |
@article{Selkoe_2003, title={N<scp>OTCH AND</scp>P<scp>RESENILIN</scp>: Regulated Intramembrane Proteolysis Links Development and Degeneration}, volume={26}, ISSN={1545-4126}, url={http://dx.doi.org/10.1146/annurev.neuro.26.041002.131334}, DOI={10.1146/annurev.neuro.26.041002.131334}, number={1}, journal={Annual Review of Neuroscience}, publisher={Annual Reviews}, author={Selkoe, Dennis and Kopan, Raphael}, year={2003}, month=mar, pages={565–597} }