Human Chorionic Gonadotropin Increases β-Cleavage of Amyloid Precursor Protein in SH-SY5Y Cells

Saberi, Soheila; Du, Yan; Christie, MacDonald J.; Goldsbury, Claire

doi:10.1007/s10571-013-9954-3

Cited by 15 publications

(9 citation statements)

References 18 publications

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“…These results are consistent with findings from studies which applied hCG to cultured cells in vitro. Addition of hCG to human embryonic stem cells caused increased expression in all forms of Aβ precursor protein (Porayette et al, 2007), while SH-SY5Y neuroblastoma cells experience increased β-cleavage when exposed to high levels of hCG (Saberi et al, 2013). A mouse model of AD (the PS1K1 line), which features a knock-in of a human mutated version of presenilin-1, a mutation highly correlated with early-onset Alzheimer's disease (Guo et al, 1999), also showed worsening of AD pathology with hCG administration.…”

Section: Role Of Lh In Alzheimer's Disease Pathology -Rodent Modelsmentioning

confidence: 98%

Luteinizing hormone as a key player in the cognitive decline of Alzheimer's disease

Burnham

Thornton

2015

Hormones and Behavior

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Section: Role Of Lh In Alzheimer's Disease Pathology -Rodent Modelsmentioning

confidence: 98%

Luteinizing hormone as a key player in the cognitive decline of Alzheimer's disease

Burnham

Thornton

2015

Hormones and Behavior

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“…Similarly, Verdile et al [62] showed that the serum levels of LH were positively correlated with the plasma Aβ levels. The possible mechanism for LH-modulated AD may be due to the fact that LH promotes the amyloidogenic pathway of the APP metabolism in which Aβs are formed [63]. …”

Section: Endocrinal Dysregulations In the Ad Pathophysiologymentioning

confidence: 99%

Role of Hypothalamic-Pituitary-Adrenal Axis, Hypothalamic-Pituitary-Gonadal Axis and Insulin Signaling in the Pathophysiology of Alzheimer’s Disease

Ahmad

Fatima

Mondal³

2019

Neuropsychobiology

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Alzheimer’s disease (AD), the commonest progressive neurodegenerative disorder of the brain, is clinically characterized by the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. Recent studies suggest a relationship between the endocrinal dysregulation and the neuronal loss during the AD pathology. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-gonadal (HPG) axis regulating circulating levels of glucocorticoid hormones has been implicated in the pathophysiology of AD. Likewise, dysregulated insulin signaling, impaired glucose uptake and insulin resistance are some of the prime factors in the onset/progression of AD. In this review, we have discussed the changes in HPA and HPG axes, implicated insulin resistance/signaling and glucose regulation during the onset/progression of AD. Therefore, simultaneous detection of these endocrinal markers in the early or presymptomatic stages may help in the early diagnosis of AD. This evidence for implicated endocrinal functions supports the fact that modulation of endocrinal pathways can be used as therapeutic targets for AD. Future studies need to determine how the induction or inhibition of endocrinal targets could be used for predictable neuroprotection in AD therapies.

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“…LH induced an increase in the generation and secretion of Aβ, coupled with decreased secretion of AβPP and increased AβPPCT100 production (sAβPPβ) in human M17 neuroblastoma cells (Bowen et al 2004b). An increase in sAβPPβ levels has also been observed in the SH-SY5Y neuroblastoma cell line following treatment with 30 mIU but not 10 mIU/ml of hCG, supporting the notion that menopausal concentrations of LH contributes to elevated Aβ levels at least in part by increasing β-cleavage of APP by β-site APP cleaving enzyme (Saberi, et al 2013). We also have determined using a developmental system of neurogenesis that hCG induces the expression of AβPP in hESC (Porayette et al 2007).…”

Section: Gonadotropins Gnrh1 and Cell Cycle Abnormalities In Alzhmentioning

confidence: 58%

The endocrine dyscrasia that accompanies menopause and andropause induces aberrant cell cycle signaling that triggers re-entry of post-mitotic neurons into the cell cycle, neurodysfunction, neurodegeneration and cognitive disease

Atwood

Bowen²

2015

Hormones and Behavior

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Sex hormones are the physiological factors that regulate neurogenesis during embryogenesis and continuing through adulthood. These hormones support the formation of brain structures such as dendritic spines, axons and synapses required for the capture of information (memories). Intriguingly, a recent animal study has demonstrated that induction of neurogenesis results in the loss of previously encoded memories in animals (e.g. infantile amnesia). In this connection, much evidence now indicates that Alzheimer’s disease (AD) also involves aberrant re-entry of post-mitotic neurons into the cell cycle. Cell cycle abnormalities appear very early in the disease, prior to the appearance of plaques and tangles, and explain the biochemical, neuropathological and cognitive changes observed with disease progression. Since sex hormones control when and how neurons proliferate and differentiate, the endocrine dyscrasia that accompanies menopause and andropause is a key signaling event that impacts neurogenesis and the acquisition, processing, storage and recall of memories. Here we review the biochemical, epidemiological and clinical evidence that alterations in endocrine signaling with menopause and andropause drive the aberrant re-entry of post-mitotic neurons into an abortive cell cycle with neurite retraction that leads to neuron dysfunction and death. When the reproductive axis is in balance, luteinizing hormone (LH), and its fetal homolog, human chorionic gonadotropin (hCG), promote pluripotent human and totipotent murine embryonic stem cell and neuron proliferation. However, strong evidence supports menopausal/andropausal elevations in the ratio of LH:sex steroids as driving aberrant mitotic events mediated by the upregulation of tumor necrosis factor, amyloid-β precursor protein processing towards the production of mitogenic Aβ, and the activation of Cdk5, a key regulator of cell cycle progression and tau phosphorylation (a cardinal feature of both neurogenesis and neurodegeneration). Cognitive studies also demonstrate the negative consequences of a high LH:sex steroid ratio on human cognitive performance. Prospective epidemiological and clinical evidence in humans supports lowering the ratio of circulating gonadotropins-GnRH to sex steroids in reducing the incidence of AD and halting cognitive decline. Together, these data support endocrine dyscrasia and the subsequent loss of cell cycle control as an important etiological event in the development of neurodegenerative diseases including AD, stroke and Parkinson’s disease.

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Human Chorionic Gonadotropin Increases β-Cleavage of Amyloid Precursor Protein in SH-SY5Y Cells

Cited by 15 publications

References 18 publications

Luteinizing hormone as a key player in the cognitive decline of Alzheimer's disease

Luteinizing hormone as a key player in the cognitive decline of Alzheimer's disease

Role of Hypothalamic-Pituitary-Adrenal Axis, Hypothalamic-Pituitary-Gonadal Axis and Insulin Signaling in the Pathophysiology of Alzheimer’s Disease

The endocrine dyscrasia that accompanies menopause and andropause induces aberrant cell cycle signaling that triggers re-entry of post-mitotic neurons into the cell cycle, neurodysfunction, neurodegeneration and cognitive disease

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