• 1
    Borchelt D.R., Thinakaran G., Eckman C.B., Lee M.K., Davenport F., Ratovitsky T., Prada C.M., Kim G., Seekins S., Yager D., Slunt H.H., Wang R., Seeger M., Levey A.I., Gandy S.E., Copeland N.G., Jenkins N.A., Price D.L., Younkin S.G., Sisodia S.S. (1996) Familial Alzheimer’s disease-linked presenilin 1 variants elevate Aβ1-42/1-40 ratio in vitro and in vivo. Neuron 17 10051013.
  • 2
    Brockhaus M., Grunberg J., Rohrig S., Loetscher H., Wittenburg N., Baumeister R., Jacobsen H., Haass C. (1998) Caspase-mediated cleavage is not required for the activity of presenilins in amyloidogenesis and NOTCH signaling. Neuroreport 9 14811486.
  • 3
    Capell A., Saffrich R., Olivo J., Meyn L., Walter J., Grunberg J., Mathews P., Nixon R., Dotti C., Haass C. (1997) Cellular expression and proteolytic processing of presenilin proteins is developmentally regulated during neuronal differentiation. J. Neurochem. 69 24322440.
  • 4
    Cook D.G., Sung J.C., Golde T.E., Felsenstein K.M., Wojczyk B.S., Tanzi R.E., Trojanowski J.Q., Lee V.M., Doms R.W. (1996) Expression and analysis of presenilin 1 in a human neuronal system: localization in cell bodies and dendrites. Proc. Natl. Acad. Sci. USA 93 92239228.
  • 5
    Doan A., Thinakaran G., Borchelt D.R., Slunt H.H., Ratovitsky T., Podlisny M., Selkoe D.J., Seeger M., Gandy S.E., Price D.L., Sisodia S.S. (1996) Protein topology of presenilin 1. Neuron 17 10231030.
  • 6
    Fraser P.E., Levesque G., Yu G., Mills L.R., Thirlwell J., Frantseva M., Gandy S.E., Seeger M., Carlen P.L., George-Hyslop P. (1998) Presenilin 1 is actively degraded by the 26S proteasome. Neurobiol. Aging 19 (Suppl.) , S19S21.
  • 7
    Ghadge G.D., Lee J.P., Bindokas V.P., Jordan J., Ma L., Miller R.J., Roos R.P. (1997) Mutant superoxide dismutase-1-linked familial amyotrophic lateral sclerosis: molecular mechanisms of neuronal death and protection. J. Neurosci. 17 87568766.
  • 8
    Goate A., Chartier-Harlin M., Mullan M., Brown J., Crawford F., Fidani L., Giuffra L., Haynes A., Irving N., James L. , et al. (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 349 704706.
  • 9
    Guo Q., Sopher B.L., Furukawa K., Pham D.G., Robinson N., Martin G.M., Mattson M.P. (1997) Alzheimer’s presenilin mutation sensitizes neural cells to apoptosis induced by trophic factor withdrawal and amyloid β-peptide: involvement of calcium and oxyradicals. J. Neurosci. 17 42124222.
  • 10
    Hartmann H., Busciglio J., Baumann K.H., Staufenbiel M., Yankner B.A. (1997) Developmental regulation of presenilin-1 processing in the brain suggests a role in neuronal differentiation. J. Biol. Chem. 272 1450514508.
  • 11
    Kim T.W., Pettingell W.H., Hallmark O.G., Moir R.D., Wasco W., Tanzi R.E. (1997a) Endoproteolytic cleavage and proteasomal degradation of presenilin 2 in transfected cells. J. Biol. Chem. 272 1100611010.
  • 12
    Kim T.W., Pettingell W.H., Jung Y.K., Kovacs D.M., Tanzi R.E. (1997b) Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease. Science 277 373376.DOI: 10.1126/science.277.5324.373
  • 13
    Lansbury P.T.J r. (1997) Structural neurology: are seeds at the root of neuronal degeneration? Neuron 19 11511154.
  • 14
    Lee M.K., Borchelt D.R., Kim G., Thinakaran G., Slunt H.H., Ratovitski T., Martin L.J., Kittur A., Gandy S., Levey A.I., Jenkins N., Copeland N., Price D.L., Sisodia S.S. (1997) Hyperaccumulation of FAD-linked presenilin 1 variants in vivo. Nat. Med. 3 756760.
  • 15
    Lehmann S., Chiesa R., Harris D.A. (1997) Evidence for a six-transmembrane domain structure of presenilin 1. J. Biol. Chem. 272 1204712051.
  • 16
    Levey A.I., Heilman C.J., Lah J.J., Nash N.R., Rees H.D., Wakai M., Mirra S.S., Rye D.B., Nochlin D., Bird T.D., Mufson E.J. (1997) Presenilin-1 protein expression in familial and sporadic Alzheimer’s disease. Ann. Neurol. 41 742753.
  • 17
    Levitan D. & Greenwald I. (1995) Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer’s disease gene. Nat. Genet. 11 219222.
  • 18
    Levitan D., Doyle T.G., Brousseau D., Lee M.K., Thinakaran G., Slunt H.H., Sisodia S.S., Greenwald I. (1996) Assessment of normal and mutant human presenilin function in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 93 1494014944.
  • 19
    Levy-Lahad E., Wasco W., Poorkaj P., Romano D.M., Oshima J., Pettingell W.H., Yu C.E., Jondro P.D., Schmidt S.D., Wang K. , et al. (1995) Candidate gene for the chromosome 1 familial Alzheimer’s disease locus. Science 269 973977.
  • 20
    Loetscher H., Deuschle U., Brockhaus M., Reinhardt D., Nelboeck P., Mous J., Grunberg J., Haass C., Jacobsen H. (1997) Presenilins are processed by caspase-type proteases. J. Biol. Chem. 272 2065520659.
  • 21
    Mann D.M., Iwatsubo T., Cairns N.J., Lantos P.L., Nochlin D., Sumi S.M., Bird T.D., Poorkaj P., Hardy J., Hutton M., Prihar G., Crook R., Rossor M.N., Haltia M. (1996) Amyloid β protein (Aβ) deposition in chromosome 14-linked Alzheimer’s disease: predominance of Aβ42(43). Ann. Neurol. 40 149156.
  • 22
    Mann D.M., Iwatsubo T., Nochlin D., Sumi S.M., Levy-Lahad E., Bird T.D. (1997) Amyloid (Aβ) deposition in chromosome 1-linked Alzheimer’s disease: the Volga German families. Ann. Neurol. 41 5257.
  • 23
    Marambaud P., Ancolio K., Lopez-Perez E., Checler F. (1998) Proteasome inhibitors prevent the degradation of familial Alzheimer’s disease-linked presenilin 1 and potentiate A beta 42 recovery from human cells. Mol. Med. 4 147157.
  • 24
    Marcuccilli C.J., Mathur S.K., Morimoto R.I., Miller R.J. (1996) Regulatory differences in the stress response of hippocampal neurons and glial cells after heat shock. J. Neurosci. 16 478485.
  • 25
    Mercken M., Takahashi H., Honda T., Sato K., Murayama M., Nakazato Y., Noguchi K., Imahori K., Takashima A. (1996) Characterization of human presenilin 1 using N-terminal specific monoclonal antibodies: evidence that Alzheimer mutations affect proteolytic processing. FEBS Lett. 389 297303.
  • 26
    Murayama O., Honda T., Mercken M., Murayama M., Yasutake K., Nihonmatsu N., Nakazato Y., Michel G., Song S., Sato K., Takahashi H., Takashima A. (1997) Different effects of Alzheimer-associated mutations of presenilin 1 on its processing. Neurosci. Lett. 229 6164.
  • 27
    Podlisny M.B., Citron M., Amarante P., Sherrington R., Xia W., Zhang J., Diehl T., Levesque G., Fraser P., Haass C., Koo E.H., Seubert P., George-Hyslop P., Teplow D.B., Selkoe D.J. (1997) Presenilin proteins undergo heterogeneous endoproteolysis between Thr291 and Ala299 and occur as stable N- and C-terminal fragments in normal and Alzheimer brain tissue. Neurobiol. Dis. 3 325337.DOI: 10.1006/nbdi.1997.0129
  • 28
    Ratovitski T., Slunt H.H., Thinakaran G., Price D.L., Sisodia S.S., Brochelt D.R. (1997) Endoproteolytic processing and stabilization of wild-type and mutant presenilin. J. Biol. Chem. 272 2453624541.
  • 29
    Sherrington R., Rogaev E.I., Liang Y., Rogaeva E.A., Levesque G., Ikeda M., Chi H., Lin C., Li G., Holman K. , et al. (1995) Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease. Nature 375 754760.
  • 30
    Shirotani K., Takahashi K., Ozawa K., Kunishita T., Tabira T. (1997) Determination of a cleavage site of presenilin 2 protein in stably transfected SH-SY5Y human neuroblastoma cell lines. Biochem. Biophys. Res. Commun. 240 728731.DOI: 10.1006/bbrc.1997.7730
  • 31
    Steiner H., Capell A., Pesold B., Citron M., Kloetzel P.M., Selkoe D.J., Romig H., Mendla K., Haass C. (1998) Expression of Alzheimer’s disease-associated presenilin-1 is controlled by proteolytic degradation and complex formation. J. Biol. Chem. 273 3232232331.
  • 32
    Strittmatter W.J., Saunders A.M., Schmechel D., Pericak-Vance M., Enghild J., Salvesen G.S., Roses A.D. (1993) Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc. Natl. Acad. Sci. USA 90 19771981.
  • 33
    Takahashi H., Mercken M., Honda T., Saito Y., Murayama M., Song S., Takashima A. (1999) Impaired proteolytic processing of presenilin-1 in chromosome 14-linked familial Alzheimer disease patient lymphocytes. Neurosci. Lett. 260 121124.
  • 34
    Takashima A. (1997) Biochemistry of presenilin 1 [in Japanese]. Rinsho Shinkeigaku 37 10971098.
  • 35
    Thinakaran G., Borchelt D.R., Lee M.K., Slunt H.H., Spitzer L., Kim G., Ratovitsky T., Davenport F., Nordstedt C., Seeger M., Hardy J., Levey A.I., Gandy S.E., Jenkins N.A., Copeland N.G., Price D.L., Sisodia S.S. (1996) Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron 17 181190.
  • 36
    Thinakaran G., Harris C.L., Ratovitski T., Davenport F., Slunt H.H., Price D.L., Borchelt D.R., Sisodia S.S. (1997) Evidence that levels of presenilins (PS1 and PS2) are coordinately regulated by competition for limiting cellular factors. J. Biol. Chem. 272 2841528422.
  • 37
    Wisniewski T., Dowjat W.K., Permanne B., Palha J., Kumar A., Gallo G., Frangione B. (1997) Presenilin-1 is associated with Alzheimer’s disease amyloid. Am. J. Pathol. 151 601610.
  • 38
    Wolozin B., Alexander P., Palacino J. (1998) Regulation of apoptosis by presenilin 1. Neurobiol. Aging 19 (Suppl.) , S23S27.
  • 39
    Xia W., Zhang J., Kholodenko D., Citron M., Podlisny M.B., Teplow D.B., Haass C., Seubert P., Koo E.H., Selkoe D.J. (1997) Enhanced production and oligomerization of the 42-residue amyloid β-protein by Chinese hamster ovary cells stably expressing mutant presenilins. J. Biol. Chem. 272 79777982.