Original article Sphingosine kinases modulate the secretion of amyloid β precursor protein from SH-SY5Y neuroblastoma cells: the role of α-synuclein

2005 ◽

Vol 33 (5) ◽

pp. 1116-1118 ◽

Cited By ~ 2

Author(s):

S.J. Patey ◽

E.A. Yates ◽

J.E. Turnbull

Keyword(s):

Amyloid Precursor Protein ◽

Heparan Sulphate ◽

Amyloid Β ◽

Precursor Protein ◽

Amyloid Β Peptide ◽

Neuritic Plaques ◽

Rate Limiting Step ◽

Aβ Amyloid ◽

Ad Alzheimer’S Disease

The role of HS (heparan sulphate) in the pathology of AD (Alzheimer's disease) is multifaceted. HS and other glycosaminoglycans have been widely reported to be associated with neuritic plaques. HS has also been shown to promote the aggregation of Aβ (amyloid β-peptide), the proteinaceous component of neuritic plaques. Recently, we described a novel and contrasting role for HS in the pathology of AD: HS can inhibit the formation of Aβ, by directly interacting with the protease BACE1 (β-site amyloid precursor protein cleaving enzyme 1; β-secretase 1), that cleaves the amyloid precursor protein and is the rate limiting step in the generation of Aβ. Here, we review the current roles of HS and the potential for HS-derivatives in the treatment of AD.

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Low density lipoprotein increases amyloid precursor protein processing to amyloidogenic pathway in differentiated SH-SY5Y cells

Biologia ◽

10.1515/biolog-2017-0024 ◽

2017 ◽

Vol 72 (2) ◽

Author(s):

Panit Yamchuen ◽

Rattima Jeenapongsa ◽

Sutisa Nudmamud-Thanoi ◽

Nanteetip Limpeanchob

Keyword(s):

Amyloid Precursor Protein ◽

Oxidized Ldl ◽

Low Density Lipoprotein ◽

Neuroblastoma Cells ◽

Density Lipoprotein ◽

Precursor Protein ◽

Amyloid Precursor Protein Processing ◽

Low Density ◽

App Processing

AbstractHypercholesterolemia has been considered as a risk factor for Alzheimer’s disease (AD). In addition to low density lipoprotein (LDL), oxidized LDL plays some roles in AD pathology. Neurodegenerative effect of oxidized LDL was supported by the increased oxidative stress in neurons. To further investigate the role of oxidized LDL, the present study aimed to test its effect on amyloid precursor protein (APP) processing. The release of soluble APP (sAPP) was evaluated in differentiated SH-SY5Y neuroblastoma cells exposed to native (non-oxidized) or oxidized human LDL including mildly and fully oxidized LDL (mox- and fox-LDL). Non-amyloidogenic and amyloidogenic pathways were investigated using specific antibody against sAPP

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Luteinizing Hormone, a Reproductive Regulator That Modulates the Processing of Amyloid-β Precursor Protein and Amyloid-β Deposition

Journal of Biological Chemistry ◽

10.1074/jbc.m311993200 ◽

2004 ◽

Vol 279 (19) ◽

pp. 20539-20545 ◽

Cited By ~ 110

Author(s):

Richard L. Bowen ◽

Giuseppe Verdile ◽

Tianbing Liu ◽

Albert F. Parlow ◽

George Perry ◽

...

Keyword(s):

Luteinizing Hormone ◽

Sex Steroids ◽

Early Adulthood ◽

Neuroblastoma Cells ◽

Amyloid Β ◽

Leuprolide Acetate ◽

Precursor Protein ◽

Aging Brain ◽

Hormonal Changes ◽

Age Related

Hormonal changes associated with the dysregulation of the hypothalamic-pituitary-gonadal (HPG) axis following menopause/andropause have been implicated in the pathogenesis of Alzheimer's disease (AD). Experimental support for this has come from studies demonstrating an increase in amyloid-β (Aβ) deposition following ovariectomy/castration. Because sex steroids and gonadotropins are both part of the HPG feedback loop, any loss in sex steroids results in a proportionate increase in gonadotropins. To assess whether Aβ generation was due to the loss of serum 17β-estradiol or to the up-regulation of serum gonadotropins, we treated C57Bl/6J mice with the anti-gonadotropin leuprolide acetate, which suppresses both sex steroids and gonadotropins. Leuprolide acetate treatment resulted in a 3.5-fold (p< 0.0001) and a 1.5-fold (p< 0.024) reduction in total brain Aβ1-42 and Aβ1-40 concentrations, respectively, after 8 weeks of treatment. To further explore the role of gonadotropins in promoting amyloidogenesis, M17 neuroblastoma cells were treated with the gonadotropin luteinizing hormone (LH) at concentrations equivalent to early adulthood (10 mIU/ml) or post-menopause/andropause (30 mIU/ml). LH did not alter amyloid-β precursor protein (AβPP) expression but did alter AβPP processing toward the amyloidogenic pathway as evidenced by increased secretion and insolubility of Aβ, decreased αAβPP secretion, and increased AβPP-C99 levels. These results suggest the marked increases in serum LH following menopause/andropause as a physiologically relevant signal that could promote Aβ secretion and deposition in the aging brain. Suppression of the age-related increase in serum gonadotropins using anti-gonadotropin agents may represent a novel therapeutic strategy for AD.

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Quercetin Disaggregates Prion Fibrils and Decreases Fibril-Induced Cytotoxicity and Oxidative Stress

Pharmaceutics ◽

10.3390/pharmaceutics12111081 ◽

2020 ◽

Vol 12 (11) ◽

pp. 1081

Author(s):

Kun-Hua Yu ◽

Cheng-I Lee

Keyword(s):

Oxidative Stress ◽

Prion Protein ◽

Amyloid Fibrils ◽

Neuroblastoma Cells ◽

Amyloid Β ◽

Transmissible Spongiform Encephalopathies ◽

Amyloid Β Peptide ◽

Hemolysis Assay ◽

Spongiform Encephalopathies

Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases caused by misfolding and aggregation of prion protein (PrP). Previous studies have demonstrated that quercetin can disaggregate some amyloid fibrils, such as amyloid β peptide (Aβ) and α-synuclein. However, the disaggregating ability is unclear in PrP fibrils. In this study, we examined the amyloid fibril-disaggregating activity of quercetin on mouse prion protein (moPrP) and characterized quercetin-bound moPrP fibrils by imaging, proteinase resistance, hemolysis assay, cell viability, and cellular oxidative stress measurements. The results showed that quercetin treatment can disaggregate moPrP fibrils and lead to the formation of the proteinase-sensitive amorphous aggregates. Furthermore, quercetin-bound fibrils can reduce the membrane disruption of erythrocytes. Consequently, quercetin-bound fibrils cause less oxidative stress, and are less cytotoxic to neuroblastoma cells. The role of quercetin is distinct from the typical function of antiamyloidogenic drugs that inhibit the formation of amyloid fibrils. This study provides a solution for the development of antiamyloidogenic therapy.

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