Secondary literature sources for A4_EXTRA
The following references were automatically generated.
- Ihara Y
- [The current status and perspectives in Alzheimer's disease research]
- Nippon Ronen Igakkai Zasshi. 2000; 37: 680-6
- Sela B
- [The complex enzymic process yielding beta-amyloid protein in Alzheimer's disease]
- Harefuah. 2000; 139: 42-7
- Higgins LS
- Animal models of Alzheimer's disease.
- Mol Med Today. 1999; 5: 274-6
- Geddes JW, Tekirian TL, Mattson MP
- N-terminus truncated beta-amyloid peptides and C-terminus truncated secreted forms of amyloid precursor protein: distinct roles in the pathogenesis of Alzheimer's disease.
- Neurobiol Aging. 1999; 20: 75-9
- Selkoe DJ
- Translating cell biology into therapeutic advances in Alzheimer's disease.
- Nature. 1999; 399: 2331-2331
- Display abstract
Studies of the molecular basis of Alzheimer's disease exemplify the increasingly blurred distinction between basic and applied biomedical research. The four genes so far implicated in familial Alzheimer's disease have each been shown to elevate brain levels of the self-aggregating amyloid-beta protein, leading gradually to profound neuronal and glial alteration, synaptic loss and dementia. Progress in understanding this cascade has helped to identify specific therapeutic targets and provides a model for elucidating other neurodegenerative disorders.
- Piekielko A
- [Proteins of Alzheimer's disease]
- Postepy Biochem. 1999; 45: 116-22
- Koudinova NV, Berezov TT, Koudinov AR
- Beta-amyloid: Alzheimer's disease and brain beta-amyloidoses.
- Biochemistry (Mosc). 1999; 64: 752-7
- Display abstract
This review considers some aspects of the biochemistry of beta-amyloid, a protein which produces insoluble deposits in the brain. These deposits are a specific morphological feature of Alzheimer's disease, Down's syndrome, and senile dementia. Our contribution to the concept of a soluble form of beta-amyloid as of a normal human protein is presented.
- Yamada T
- [Molecular physiopathology of Alzheimer's disease]
- Fukuoka Igaku Zasshi. 1998; 89: 29-33
- Iwatsubo T, Tomita T
- [Genetic factors in the pathogenesis of Alzheimer's disease: roles of beta-amyloid and presenilins]
- Tanpakushitsu Kakusan Koso. 1998; 43: 1963-72
- Gui L, Li W
- [Amyloid protein precursor gene and neuron apoptosis of Alzheimer's disease]
- Zhonghua Yi Xue Za Zhi. 1998; 78: 582-3
- Yamazaki T
- [Alzheimer's disease]
- Tanpakushitsu Kakusan Koso. 1997; 42: 2393-8
- Tienari PJ et al.
- Neuronal sorting and processing of amyloid precursor protein: implications for Alzheimer's disease.
- Cold Spring Harb Symp Quant Biol. 1996; 61: 575-85
- Bao X
- Beta-amyloid protein and Alzheimer's disease.
- Chin Med J (Engl). 1996; 109: 41-3
- Mera SL
- Alzheimer's disease: genetics or environment?
- Br J Biomed Sci. 1996; 53: 91-2
- An ZP, Cheng S
- [beta-Amyloid protein and Alzheimer's disease]
- Sheng Li Ke Xue Jin Zhan. 1996; 27: 350-2
- Nitsch RM
- From acetylcholine to amyloid: neurotransmitters and the pathology of Alzheimer's disease.
- Neurodegeneration. 1996; 5: 477-82
- Display abstract
Brain amyloid deposits play a central role in the histopathology of Alzheimer's disease (AD), as evidenced by increased formation of amyloid beta peptides (A beta) in genetic forms of AD that are caused by mutations in the presenilin genes, or the amyloid beta protein precursor (APP) gene. Neuronal deafferentation in AD brain may also be associated with accelerated A beta formation, because APP processing is regulated by neuronal activity, presumably via several G protein-coupled neurotransmitter receptors. Subtype-selective agonists including muscarinic m1 receptor ligands may be useful for the pharmacological reduction of A beta formation.
- Tamaoka A, Kametani F
- [APP, the causal gene for Alzheimer's disease]
- Tanpakushitsu Kakusan Koso. 1996; 41: 1453-9
- Beyreuther K, Multhaup G, Masters CL
- Alzheimer's disease: genesis of amyloid.
- Ciba Found Symp. 1996; 199: 119-27
- Display abstract
Much of the present knowledge on the genes and genetic processes involved in the genesis of amyloid formation in Alzheimer's disease (AD) has come directly or indirectly from the retrospective molecular and genetic analysis of amyloid beta-protein (A beta or beta A4) deposits and from the identification of genes involved in inherited susceptibility to the disease. This analysis shows that the release and aggregation of the A beta fragment from the amyloid precursor protein (APP) is involved in APP (AD1), chromosome 14 (AD3), 1 (AD4) and 19(AD2) families as well as in the sporadic forms of AD, suggesting that AD is a single disease with a common APP/A beta amyloid pathogenesis. Synthetic A beta protein readily forms beta sheets, filaments and amyloid at micromolar concentrations. The principle to inhibit this process has been worked out by our groups with A beta variants. The N-terminal and C-terminal A beta sequences, oxidative radicals, membrane integrity and metal ions also affect the aggregation of A beta. Amino acid substitutions within the A beta sequence, as occur in rodents, alter A beta release and change the degree to which oxidation of the peptides occurs. Transgenic approaches resulting in overexpression of human APP have confirmed that A beta sequence and concentration are critical prerequisites to amyloid deposition in vivo.
- Hendriks L, Jonghe CDXs, Cras P, Martin JJ, Broeckhoven CV
- Beta-amyloid precursor protein and early-onset Alzheimer's disease.
- Ciba Found Symp. 1996; 199: 170-80
- Display abstract
One of the major pathological hallmarks of Alzheimer's disease is the deposition in the brain parenchyma and cerebral blood vessel walls of amyloid beta-protein, a 4kDa proteolytic product of the longer beta-amyloid precursor protein (APP). Six different single base mutations in the APP gene have been reported causing early-onset Alzheimer's disease (age at onset < or = 65 years) or related amyloidosis in a small number of families. Cell transfection experiments using wild-type and mutant APP cDNA indicated that APP mutations result in the production of more or longer, aggregation prone, A beta peptides.
- Neve RL
- Mixed signals in Alzheimer's disease.
- Trends Neurosci. 1996; 19: 371-2
- Masters CL, Beyreuther K
- Molecular neuropathology of Alzheimer's disease.
- Arzneimittelforschung. 1995; 45: 410-2
- Display abstract
Alzheimer's disease (AD) is caused by the aberrant metabolism of the amyloid precursor protein (APP) and is consequently associated with the accumulation of one of its degradation products, the beta A4 amyloid protein. The proteases (secretases) which generate beta A4 from APP are now being defined, as is the normal function of APP. How neurons degenerate in AD remains unexplained, but is of central importance in developing new therapeutic approaches. While the genetic factors which contribute to the aberrant metabolism of APP are now being elucidated, the environmental factors which exacerbate this process are unknown.
- Citron M, Teplow DB, Selkoe DJ
- Generation of amyloid beta protein from its precursor is sequence specific.
- Neuron. 1995; 14: 661-70
- Display abstract
Cerebral deposition of amyloid beta protein (A beta) is an early and critical feature of Alzheimer's disease. Here we analyze the substrate requirements of proteases ("beta-secretases") that cleave the beta-amyloid precursor protein (beta APP) at the N-terminus of A beta (Asp-597 of beta APP695) in intact human cells. The cleavage requires a membrane-bound substrate but tolerates shifts in the distance of the hydrolyzed bond from the membrane. The major protease has a minimum recognition region of Val-594 to Ala-598; most substitutions in this sequence strongly decrease or eliminate A beta production. Only the Swedish familial Alzheimer's disease mutation (K595N/M596L) strongly increases A beta production. Moreover, in this mutant but not in the wild type, the entire cytoplasmic tail with its reinternalization signals can be deleted without affecting A beta N-terminal cleavage, consistent with the concept that cleavage of this mutant occurs in a different cellular compartment than that of wild-type molecules. Our results have important implications for current intensive approaches to develop assays for and identify enzymes with beta-secretase activity.
- Checler F
- Processing of the beta-amyloid precursor protein and its regulation in Alzheimer's disease.
- J Neurochem. 1995; 65: 1431-44
- Richards SJ, Hodgman C, Sharpe M
- Reported sequence homology between Alzheimer amyloid770 and the MRC OX-2 antigen does not predict function.
- Brain Res Bull. 1995; 38: 305-6
- Larner AJ
- Catastrophe and Alzheimer's disease.
- J R Coll Physicians Lond. 1995; 29: 549-549
- Charnay Y, Vallet PG, Giannakopoulos P, Hof PR, Bouras C
- [Molecular biology of beta A4 protein and Alzheimer disease]
- Rev Neurol (Paris). 1994; 150: 405-12
- Display abstract
Senile plaques, neurofibrillary tangles and neuronal loss are the major histopathologic hallmarks of Alzheimer's disease. A prominent component of the senile plaques is a polypeptide (beta A4) of about 40 amino acids derived via proteolytic cleavage from a set of larger protein isoforms collectively referred to as the amyloid precursor protein (APP). The protein APP is a widely distributed transmembrane glycoprotein structurally related to a cell surface receptor. APP is encoded by a single gene on chromosome 21 in which missense mutations have been demonstrated in several cases of familial Alzheimer's disease. It is thought that various factors fostering the APP-processing pathway by which the polypeptide beta A4 is generated might be pathogenic. Thus the mechanisms that govern the rate of transcription of the APP gene, the differential splicing of the precursor messenger and the proteolytic processing of APP are current subjects of intensive investigation. Theoretically, each of these events represents a potential target for a therapeutic intervention. However, the relationships between amyloidogenesis and the formation of the neurofibrillary tangles associated to the neuronal loss remain to be elucidated.
- Cordell B
- beta-Amyloid formation as a potential therapeutic target for Alzheimer's disease.
- Annu Rev Pharmacol Toxicol. 1994; 34: 69-89
- Gandy S, Greengard P
- Processing of Alzheimer A beta-amyloid precursor protein: cell biology, regulation, and role in Alzheimer disease.
- Int Rev Neurobiol. 1994; 36: 29-50
- Masters CL, Beyreuther K
- Alzheimer's disease: a clearer definition of the genetic components.
- Med J Aust. 1994; 160: 243-4
- Selkoe DJ
- Alzheimer's disease: a central role for amyloid.
- J Neuropathol Exp Neurol. 1994; 53: 438-47
- Selkoe DJ
- Cell biology of the amyloid beta-protein precursor and the mechanism of Alzheimer's disease.
- Annu Rev Cell Biol. 1994; 10: 373-403
- LeBlanc A
- The role of beta-amyloid peptide in Alzheimer's disease.
- Metab Brain Dis. 1994; 9: 3-31
- Selkoe DJ
- Normal and abnormal biology of the beta-amyloid precursor protein.
- Annu Rev Neurosci. 1994; 17: 489-517
- Kosik KS
- The Alzheimer's disease sphinx: a riddle with plaques and tangles.
- J Cell Biol. 1994; 127: 1501-4
- Fraser PE, Levesque L, McLachlan DR
- Biochemistry of Alzheimer's disease amyloid plaques.
- Clin Biochem. 1993; 26: 339-49
- Display abstract
One of the principal identifying features of Alzheimer's disease (AD) is the extracellular deposition of fibrous protein aggregates in the form of amyloid plaques. The major component of these deposits is the amyloid beta (A beta) protein that is a proteolytic fragment of the integral membrane amyloid precursor protein (APP). Understanding the pathways responsible for A beta formation and the mechanism by which it accumulates within the brain could provide key answers to AD pathogenesis. This review will explore the biochemistry of A beta and its precursor, the possible causal relationship between amyloid and AD-associated neuronal death, the role of additional cellular elements in amyloid formation, and the potential application of these components in clinical diagnosis.
- Rosenberg RN
- A causal role for amyloid in Alzheimer's disease: the end of the beginning.
- Neurology. 1993; 43: 851-6
- Hirai S, Okamoto K
- [Beta/A4-type amyloid protein in Alzheimer's disease and cerebral amyloid angiopathies]
- Nippon Naika Gakkai Zasshi. 1993; 82: 1424-9
- Ward D
- Models of APP dysfunction in Alzheimer's disease.
- Biochem Soc Trans. 1993; 21: 55-55
- Chen SD, Fang JJ
- [Amyloid precursor protein and Alzheimer's disease]
- Sheng Li Ke Xue Jin Zhan. 1993; 24: 306-9
- Selkoe DJ
- Physiological production of the beta-amyloid protein and the mechanism of Alzheimer's disease.
- Trends Neurosci. 1993; 16: 403-9
- Display abstract
The progressive deposition of the beta-amyloid peptide in the brain and its microvasculature is an invariant feature of Alzheimer's disease that appears to precede the onset of dementia by many years. It had been assumed that the proteolytic release of beta-amyloid peptide from the transmembrane region of its large precursor protein was an aberrant event, requiring prior membrane injury. However, it has recently been shown that beta-amyloid peptide is continuously secreted from healthy neural and non-neural cells in culture and circulates in human CSF and blood. The finding that beta-amyloid peptide is a normal, soluble product of cellular metabolism has led to many dynamic studies of its formation and clearance in health and in genetic forms of Alzheimer's disease, and should facilitate the design of amyloid-inhibiting therapeutics.
- Rossor MN
- Molecular pathology of Alzheimer's disease.
- J Neurol Neurosurg Psychiatry. 1993; 56: 583-6
- Tsuji S
- [Molecular genetics of Alzheimer's disease]
- Seikagaku. 1993; 65: 1-7
- Haass C, Selkoe DJ
- Cellular processing of beta-amyloid precursor protein and the genesis of amyloid beta-peptide.
- Cell. 1993; 75: 1039-42
- Ishiura S
- [Alzheimer's disease amyloid A4(beta) protein]
- Tanpakushitsu Kakusan Koso. 1990; 35: 1517-24
- de Sauvage F, Octave JN
- A novel mRNA of the A4 amyloid precursor gene coding for a possibly secreted protein.
- Science. 1989; 245: 651-3
- Display abstract
The gene, encoding the A4 peptide found in the amyloid core of senile plaques isolated from the cerebral cortex of patients with Alzheimer's disease, produces at least three precursors that resemble cell surface receptors. A clone isolated from a human brain complementary DNA library contained the structural sequence for an A4 amyloid peptide precursor with a serine protease inhibitor domain in which 208 amino acids at the carboxyl terminal are replaced by 20 amino acids derived from nucleotide sequences with homology to the Alu repeat family. This protein devoid of the transmembrane domain most likely represents a secreted form of the A4 amyloid peptide precursor.
- Lemaire HG et al.
- The PreA4(695) precursor protein of Alzheimer's disease A4 amyloid is encoded by 16 exons.
- Nucleic Acids Res. 1989; 17: 517-22
- Display abstract
Alzheimer's disease (AD) is characterized by the cerebral deposition of fibrillar aggregates of the amyloid A4 protein. Complementary DNA's coding for the precursor of the amyloid A4 protein have been described. In order to identify the structure of the precursor gene relevant clones from several human genomic libraries were isolated. Sequence analysis of the various clones revealed 16 exons to encode the 695 residue precursor protein (PreA4(695] of Alzheimer's disease amyloid A4 protein. The DNA sequence coding for the amyloid A4 protein is interrupted by an intron. This finding supports the idea that amyloid A4 protein arises by incomplete proteolysis of a larger precursor, and not by aberrant splicing.
- Kang J, Muller-Hill B
- The sequence of the two extra exons in rat preA4.
- Nucleic Acids Res. 1989; 17: 2130-2130
- Chou WG et al.
- Extracytoplasmic and A4 domains of the amyloid precursor protein: molecular cloning, genetically engineered cell lines and immunocytochemical investigations.
- Prog Clin Biol Res. 1989; 317: 991-9
- Marotta CA, Chou WG, Majocha RE, Watkins R, LaBonne C, Zain SB
- Overexpression of amyloid precursor protein A4 (beta-amyloid) immunoreactivity in genetically transformed cells: implications for a cellular model of Alzheimer amyloidosis.
- Proc Natl Acad Sci U S A. 1989; 86: 337-41
- Display abstract
Among the major obstacles to clarifying molecular mechanisms involved in amyloid metabolism in Alzheimer disease has been the unavailability of laboratory models for this uniquely human disorder. The present studies were aimed at establishing genetically engineered cell lines that overexpress amyloid immunoreactivity and that may be relevant to amyloid accumulation in the Alzheimer disease brain. We used cloned amyloid cDNA that contains a region encoding A4 (beta-polypeptide) amino acids along with recently developed tumor virus vectors derived from simian virus 40 to prepare transformed cells. After transient and permanent transfection, a variety of cell types overexpressed A4 immunoreactivity that was detected by highly specific monoclonal antibodies. We observed that the use of an amyloid subdomain containing the A4 region, but lacking the sequence of a Kunitz-type protease inhibitor found in amyloid precursor protein variants, was sufficient to obtain cells that overproduced an A4 epitope. The transformed cells were readily propagated in culture and may provide an experimental medium to elucidate aspects of the molecular pathogenesis of Alzheimer disease. The cellular models may also serve as tools for deriving potentially useful therapeutic agents.
- Shivers BD, Hilbich C, Multhaup G, Salbaum M, Beyreuther K, Seeburg PH
- Alzheimer's disease amyloidogenic glycoprotein: expression pattern in rat brain suggests a role in cell contact.
- EMBO J. 1988; 7: 1365-70
- Display abstract
The cloned cDNA encoding the rat cognate of the human A4 amyloid precursor protein was isolated from a rat brain library. The predicted primary structure of the 695-amino acid-long protein displays 97% identity to its human homologue shown previously to resemble an integral membrane protein. The protein was detected in rodent brain and muscle by Western blot analysis. Using in situ hybridization and immunocytochemistry on rat brain sections, we discovered that rat amyloidogenic glycoprotein (rAG) and its mRNA are ubiquitously and abundantly expressed in neurons indicating a neuronal original for the amyloid deposits observed in humans with Alzheimer's disease (AD). The protein appears in patches on or near the plasma membranes of neurons suggesting a role for this protein in cell contact. Highest expression was seen in rat brain regions where amyloid is deposited in AD but also in areas which do not contain deposits in AD. Since amyloid deposits are rarely observed in rat brain, we conclude that high expression of AG is not the sole cause of amyloidosis.
- Zimmermann K et al.
- Localization of the putative precursor of Alzheimer's disease-specific amyloid at nuclear envelopes of adult human muscle.
- EMBO J. 1988; 7: 367-72
- Display abstract
Cloning and sequence analysis revealed the putative amyloid A4 precursor (pre-A4) of Alzheimer's disease to have characteristics of a membrane-spanning glycoprotein. In addition to brain, pre-A4 mRNA was found in adult human muscle and other tissues. We demonstrate by in situ hybridization that pre-A4 mRNA is present in adult human muscle, in cultured human myoblasts and myotubes. Immunofluorescence with antipeptide antibodies shows the putative pre-A4 protein to be expressed in adult human muscle and associated with some but not all nuclear envelopes. Despite high levels of a single 3.5-kb pre-A4 mRNA species in cultured myoblasts and myotubes, the presence of putative pre-A4 protein could not be detected by immunofluorescence. This suggests that putative pre-A4 protein is stabilized and therefore functioning in the innervated muscle tissue but not in developing, i.e. non-innervated cultured muscle cells. The selective localization of the protein on distinct nuclear envelopes could reflect an interaction with motor endplates.
- Kang J et al.
- The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor.
- Nature. 1987; 325: 733-6
- Display abstract
Alzheimer's disease is characterized by a widespread functional disturbance of the human brain. Fibrillar amyloid proteins are deposited inside neurons as neurofibrillary tangles and extracellularly as amyloid plaque cores and in blood vessels. The major protein subunit (A4) of the amyloid fibril of tangles, plaques and blood vessel deposits is an insoluble, highly aggregating small polypeptide of relative molecular mass 4,500. The same polypeptide is also deposited in the brains of aged individuals with trisomy 21 (Down's syndrome). We have argued previously that the A4 protein is of neuronal origin and is the cleavage product of a larger precursor protein. To identify this precursor, we have now isolated and sequenced an apparently full-length complementary DNA clone coding for the A4 polypeptide. The predicted precursor consists of 695 residues and contains features characteristic of glycosylated cell-surface receptors. This sequence, together with the localization of its gene on chromosome 21, suggests that the cerebral amyloid deposited in Alzheimer's disease and aged Down's syndrome is caused by aberrant catabolism of a cell-surface receptor.
