A? peptides and calcium influence secretion of the amyloid protein precursor from chick sympathetic neurons in culture

Mok, Su San; Clippingdale, Andrew B.; Beyreuther, Konrad; Masters, Colin L.; Barrow, Colin J.; Small, David H.

doi:10.1002/1097-4547(20000815)61:4<449::aid-jnr12>3.0.co;2-n

Cited by 14 publications

(13 citation statements)

References 78 publications

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“…One is the separation of its two negative charges by a fixed distance and the other is the biaryl core organic framework. Titration of radiolabeled CR with A 40 aggregates gave Kd values ranging from 1,100 to 1,500 nM, which are lower than those from a radioligand assay (Ki around 8,000 nM) performed with slightly different A [34][35][36][37][38][39][40][41][42] aggregates. However, when the reference radioligand is changed to chrysamine G (CG; 18), the Ki value of CR changes to 48 nM, representing more than 20-fold higher affinity.…”

Section: Congo Red (Cr) Type Ligandsmentioning

confidence: 99%

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Radioligand Development for PET Imaging of β-Amyloid (Aβ)-Current Status

Cai

Innis²,

Pike³

2007

CMC

128

121

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Two of the main pathological hallmarks of Alzheimer's disease (AD) are neuritic plaques and neurofibrillary tangles. Significant evidence supports a critical and probable causative role of amyloid (A ) plaque formation. Since neuroprotective treatments are typically most effective at early stages of injury, the detection and measurement of A load in living brain should be performed at early and perhaps even presymptomatic stages of AD. Two primary targets of molecular imaging research with positron emission tomography (PET) are to develop surrogate markers (radioligands) for assessing disease progression and for monitoring the efficacy of developmental therapeutics. Here, we review the current status of radioligand development for PET imaging of A aggregates. General structure-activity relationships have emerged, including the identification of at least three different ligand binding sites in various A aggregates and recognition of the general structural requirements for ligand binding at each site. Also a few radioligands applicable to imaging A plaques in living human brain with positron emission tomography (PET) have emerged, including [ 11 C]PIB, [ 11 C]SB-13 and [ 18 F]FDDNP.

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Section: Congo Red (Cr) Type Ligandsmentioning

confidence: 99%

“…A precipitation is considered to result from either its over-production or its slow digestion. The accumulation of A in the AD brain reduces secretion of APP [34]. Since secreted APP has been proposed to have a neuroprotective function, A deposits may thereby indirectly increase A toxicity.…”

Section: Introduction To Alzheimer's Disease (Ad)mentioning

confidence: 99%

Radioligand Development for PET Imaging of β-Amyloid (Aβ)-Current Status

Cai

Innis²,

Pike³

2007

CMC

128

121

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“…Because ␣-secretase destroys the A␤ sequence, it is generally thought that ␣-secretase pathway mitigates amyloid formation, although this has not yet been demonstrated unequivocally (40). In addition, the C-terminally truncated form of APP released by ␣-secretase may have trophic actions (41), which could antagonize the neurotoxic effects of aggregated A␤ (42). ACE acts like the ␣-secretase in degrading A␤ and thus preventing aggregation.…”

mentioning

confidence: 99%

“…BACE can cleave full-length APP at Asp 1 of the A␤ sequence and also at Glu 11 (42). Recently, Chesneau et al (43) reported that insulin-degrading enzyme (IDE) is sufficient to degrade A␤ and that its degradation products do not promote oligomerization of the intact A␤ peptide (43).…”

mentioning

confidence: 99%

Angiotensin-converting Enzyme Degrades Alzheimer Amyloid β-Peptide (Aβ); Retards Aβ Aggregation, Deposition, Fibril Formation; and Inhibits Cytotoxicity

Hu¹,

Igarashi²,

Kamata³

et al. 2001

Journal of Biological Chemistry

329

218

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We have demonstrated that the angiotensin-converting enzyme (ACE) genotype is associated with Alzheimer's disease (AD) in the Japanese population (1). To determine why ACE affects susceptibility to AD, we examined the effect of purified ACE on aggregation of the amyloid ␤-peptide (A␤) in vitro. Surprisingly, ACE was found to significantly inhibit A␤ aggregation in a dose response manner. The inhibition of aggregation was specifically blocked by preincubation of ACE with an ACE inhibitor, lisinopril. ACE was confirmed to retard A␤ fibril formation with electron microscopy. ACE inhibited A␤ deposits on a synthaloid plate, which was used to monitor A␤ deposition on autopsied brain tissue. ACE also significantly inhibited A␤ cytotoxicity on PC12 h. The most striking fact was that ACE degraded A␤ by cleaving A␤-(1-40) at the site Asp 7 -Ser 8 . This was proven with reverse-phase HPLC, amino acid sequence analysis, and MALDI-TOF/MS. Compared with A␤-(1-40), aggregation and cytotoxic effects of the degradation products A␤-(1-7) and A␤-(8 -40) peptides were reduced or virtually absent. These findings led to the hypothesis that ACE may affect susceptibility to AD by degrading A␤ and preventing the accumulation of amyloid plaques in vivo.Progressive cerebral dysfunction in Alzheimer's disease (AD) 1 is accompanied by innumerable extracellular amyloid deposits in the form of senile plaque and microvascular amyloid. Amyloid protein is derived from the integral membrane polypeptide, ␤-amyloid precursor protein (␤APP). The released 39 -43 residue amyloid ␤-peptide (A␤) may subsequently undergo aggregation to form amyloid fibrils under the influence of various amyloid-associated factors (2). The aggregation and deposition of A␤ has been linked to the toxic effects causing cell damage in AD. Because A␤ is present in both normal and AD subjects, an answer to the question of why A␤ accumulates in AD but not in the normal brain may lead to a possible cure for AD.Angiotensin-converting enzyme (ACE; dipeptidyl carboxypeptidase, EC 3.4.15.1) is a membrane-bound ectoenzyme. It catalyzes the conversion of angiotensin I (AngI) to angiotensin II (AngII), which plays an important role in blood pressure and body fluid and sodium homeostasis (3). The cloning of the ACE gene revealed a 287-bp insertion (I)/deletion (D) polymorphism in intron 16. The serum ACE activity of the ACE DD genotype was twice as high as that of the ACE II genotype (4). The ACE genotype is considered to be associated with hypertension, coronary artery disease, left ventricular hypertrophy, myocardial infarction, and diabetic nephropathy (5-7). In particular, the ACE DD genotype is considered to be a risk factor for vascular diseases.We have compared the distribution of an I/D polymorphism of the gene coding for ACE in 133 Japanese sporadic AD patients and 257 control subjects (1). The association between AD and ACE genotypes or alleles was found to be significant. The frequency of the ACE II genotype was 1.4ϫ higher in AD than in controls, whereas that of ACE DD gen...

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“…It is assumed that α-secretase pathway reduces production of amyloid plaques however it has not been yet clearly demonstrated. In addition sAPPα, which is released by α-secretase, has trophic effects (Esch et al, 1990) which can act against neurotoxic effects of aggregated A (Mok et al, 2000). The localisation of α-secretase is unknown.…”

Section: Amyloid Precursor Proteinmentioning

confidence: 99%

Alzheimer's Disease: Definition, Molecular and Genetic Factors

Babušíková¹,

Evinová²,

Jurečeková³

et al. 2011

Advanced Understanding of Neurodegenerative Diseases

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A? peptides and calcium influence secretion of the amyloid protein precursor from chick sympathetic neurons in culture

Cited by 14 publications

References 78 publications

Radioligand Development for PET Imaging of β-Amyloid (Aβ)-Current Status

Radioligand Development for PET Imaging of β-Amyloid (Aβ)-Current Status

Angiotensin-converting Enzyme Degrades Alzheimer Amyloid β-Peptide (Aβ); Retards Aβ Aggregation, Deposition, Fibril Formation; and Inhibits Cytotoxicity

Alzheimer's Disease: Definition, Molecular and Genetic Factors

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A? peptides and calcium influence secretion of the amyloid protein precursor from chick sympathetic neurons in culture

Cited by 14 publications

References 78 publications

Radioligand Development for PET Imaging of &#946;-Amyloid (A&#946;)-Current Status

Radioligand Development for PET Imaging of &#946;-Amyloid (A&#946;)-Current Status

Angiotensin-converting Enzyme Degrades Alzheimer Amyloid β-Peptide (Aβ); Retards Aβ Aggregation, Deposition, Fibril Formation; and Inhibits Cytotoxicity

Alzheimer's Disease: Definition, Molecular and Genetic Factors

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Radioligand Development for PET Imaging of β-Amyloid (Aβ)-Current Status

Radioligand Development for PET Imaging of β-Amyloid (Aβ)-Current Status