Human cortical neuronal (HCN) cell lines: a model for amyloid β neurotoxicity

Zhang, Zhiyuan; Drzewiecki, Gary J.; Hom, Joanne T.; May, Patrick C.; Hyslop, Paul A.

doi:10.1016/0304-3940(94)90892-3

Cited by 25 publications

(12 citation statements)

References 14 publications

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“…These findings support the contention that cholinergic neurons are particularly vulnerable in AD brain (15) and are consistent with the importance of AcCho in memory and learning processes (16,17). Peptides derived from the human AP sequence have been shown to cause toxic effects in cell lines and primary cultures of neuronal origin (18)(19)(20)(21)(22)(23) as well as in vivo (24,25). Moreover, injections of A13 1-40 or A,B 1-42 into the nucleus basalis magnocellularis or the medial septum of the rat brain cause neurodegeneration and reductions in the levels of cholinergic markers (26)(27)(28).…”

supporting

confidence: 82%

Amyloid beta-protein reduces acetylcholine synthesis in a cell line derived from cholinergic neurons of the basal forebrain.

Pedersen

Kłoczewiak

Blusztajn

1996

Proc. Natl. Acad. Sci. U.S.A.

123

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The characteristic features of a brain with Alzheimer disease (AD) include the presence of neuritic plaques composed of amyloid 3-protein (A,B) and reductions in the levels of cholinergic markers. Neurotoxic responses to A,B have been reported in vivo and in vitro, suggesting that the cholinergic deficit in AD brain may be secondary to the degeneration of cholinergic neurons caused by Aj8. However, it remains to be determined if A,B contributes to the cholinergic deficit in AD brain by nontoxic effects. We examined the effects of synthetic A,B peptides on the cholinergic properties of a mouse cell line, SN56, derived from basal forebrain cholinergic neurons. Aj8 1-42 and Aj3 1-28 reduced the acetylcholine (AcCho) content of the cells in a concentrationdependent fashion, whereas Af3 1-16 was inactive. Maximal reductions of 43% and 33% were observed after a 48-h treatment with 100 nM of A18 1-42 and 50 pM of A18 1-28, respectively. Neither A,B 1-28 nor A,B 1-42 at a concentration of 100 nM and a treatment period of 2 weeks was toxic to the cells. Treatment of the cells with A,B 25-28 (48 h; 100 nM) significantly decreased AcCho levels, suggesting that the sequence GSNK (aa 25-28) is responsible for the AcChoreducing effect of Af3. The reductions in AcCho levels caused by A,B 1-42 and Af3 1-28 were accompanied by proportional decreases in choline acetyltransferase activity. In contrast, acetylcholinesterase activity was unaltered, indicating that A18 specifically reduces the synthesis of AcCho in SN56 cells. The reductions in AcCho content caused by AfJ 1-42 could be prevented by a cotreatment with all-trans-retinoic acid (10 nM), a compound previously shown to increase choline acetyltransferase mRNA expression in SN56 cells. These results demonstrate a nontoxic, suppressive effect of A,B on AcCho synthesis, an action that may contribute to the cholinergic deficit in AD brain.An invariant pathological feature of a brain with Alzheimer disease (AD) is the formation of the neuritic plaque, a compacted extracellular deposit of amyloid filaments surrounded by dystrophic neurites (1). This amyloid is composed of the --4-kDa amyloid 13-protein (A13), which is proteolytically derived from a 110-130 kDa transmembrane glycoprotein known as the ,B-amyloid precursor protein (,BAPP) (1). Heterogeneous processing of 1APP results in the formation of A,B peptides ranging from 39 to 43 amino acids in length (1). Several missense mutations in the j3APP gene have been linked to familial AD (2-4), and some of these have been shown to result either in excess generation of AP3 (5-7) or in a shift to the production of longer, more amyloidogenic forms (8).Overexpression of the PAPP gene, which is located on the long arm of chromosome 21, occurs in Down syndrome (trisomy 21) patients, essentially all of whom exhibit AD brain pathology by the age of 40 (9). Furthermore, transgenic mice overexpressing a mutated human ,BAPP gene display many of the pathological features of AD brain, including the neuritic plaque (10). These observati...

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supporting

confidence: 82%

Amyloid beta-protein reduces acetylcholine synthesis in a cell line derived from cholinergic neurons of the basal forebrain.

Pedersen

Kłoczewiak

Blusztajn

1996

Proc. Natl. Acad. Sci. U.S.A.

123

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“…Second, amyloid deposition temporally precedes the development of neurofibrillary changes (Pappolla and Robakis, 1995), and this observation is also consistent with a link between amyloid and neuronal degeneration. Finally, it has been shown that A␤ is toxic to neurons (Yankner et al, 1990;Behl et al, 1992Behl et al, , 1994aZhang et al, 1994), a finding that also strengthens the notion that the amyloid peptide may contribute to the neuronal pathology in AD.…”

supporting

confidence: 60%

Melatonin Prevents Death of Neuroblastoma Cells Exposed to the Alzheimer Amyloid Peptide

et al. 1997

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Studies from several laboratories have generated evidence suggesting that oxidative stress is involved in the pathogenesis of Alzheimer's disease (AD). The finding that the amyloid ␤ protein (A␤) has neurotoxic properties and that such effects are, in part, mediated by free radicals has provided insights into mechanisms of cell death in AD and an avenue to explore new therapeutic approaches. In this study we demonstrate that melatonin, a pineal hormone with recently established antioxidant properties, is remarkably effective in preventing death of cultured neuroblastoma cells as well as oxidative damage and intracellular Ca 2ϩ increases induced by a cytotoxic fragment of A␤. The effects of melatonin were extremely reproducible and corroborated by multiple quantitative methods, including cell viability studies by confocal laser microscopy, electron microscopy, and measurements of intracellular calcium levels. The importance of this finding is that, in contrast to conventional antioxidants, melatonin has a proposed physiological role in the aging process. Secretion levels of this hormone are decreased in aging and more severely reduced in AD. The reported phenomenon may be of therapeutic relevance in AD.

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“…When differentiated, HCN2 cells extend long, branched processes resembling mature neurons. The HCN2 cell line has been used as a cell culture model to study β-amyloid neurotoxicity [43].…”

mentioning

confidence: 99%

A Review of the Regulatory Role of Nicotinamide on Pro- and Anti-apoptotic Proteins in Neuronal Cells

Mukherjee¹,

Sonee²,

Adams³

2005

LDDD

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Numerous studies have shown that nicotinamide can prevent cell death via both necrosis and apoptosis. DNA fragmentation, NAD, poly(ADP-ribose) polymerase, apoptosis inducing factors, tumor necrosis factors, p53, caspases, inhibitor of apoptosis proteins and other factors are important in the action of nicotinamide. In this review, the regulatory effect of nicotinamide on individual pro-and anti-apoptotic proteins in neuronal cells have been delineated with a view to present a central molecular mechanism by which nicotinamide prevents apoptosis in the brain.

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Human cortical neuronal (HCN) cell lines: a model for amyloid β neurotoxicity

Cited by 25 publications

References 14 publications

Amyloid beta-protein reduces acetylcholine synthesis in a cell line derived from cholinergic neurons of the basal forebrain.

Amyloid beta-protein reduces acetylcholine synthesis in a cell line derived from cholinergic neurons of the basal forebrain.

Melatonin Prevents Death of Neuroblastoma Cells Exposed to the Alzheimer Amyloid Peptide

A Review of the Regulatory Role of Nicotinamide on Pro- and Anti-apoptotic Proteins in Neuronal Cells

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