Lovastatin protects human neurons against Aβ-induced toxicity and causes activation of β-catenin–TCF/LEF signaling

Salins, Pradeep; Shawesh, Salim; He, Yang; Dibrov, Alexander; Kashour, Tarek; Arthur, Gilbert; Amara, Francis M.

doi:10.1016/j.neulet.2006.07.045

Cited by 46 publications

(42 citation statements)

References 22 publications

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“…A number of alternatives are being explored towards increasing -catenin expression to promote Wnt signaling [73]. In our study we showed that statins act by blocking the activity and expression of GSK-3 , thereby increasing -catenin levels.…”

Section: Anti-apoptotic Signaling Pathways Of Statins In Admentioning

confidence: 68%

“…3). It is likely that statins could potentiate the activation of many pro-survival pathways, however, the activation of only a few pro-survival pathways have been demonstrated in neuronal systems [73]. Other pro-survival activation has been demonstrated using cardiac and stem cells [74].…”

Section: Anti-apoptotic Signaling Pathways Of Statins In Admentioning

confidence: 99%

“…Wnt signaling is neuroprotective against the toxic effects of A induced neurotoxicity [73]. Wnt's are secreted cysteine-rich glycoproteins that bind to frizzled receptors and mediate cell-signaling [75].…”

Section: Anti-apoptotic Signaling Pathways Of Statins In Admentioning

confidence: 99%

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Neuroprotective Role of Statins in Alzheimer`s Disease: Anti-Apoptotic Signaling~!2009-02-06~!2010-04-04~!2010-06-22~!

Hunt¹,

Salins²,

Anderson³

et al. 2010

TONEURJ

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Alzheimer's disease (AD), a severe form of senile dementia is a neurodegenerative disorder. One of the most well characterized hallmarks of AD are extra-neuronal aggregates of amyloid-beta peptide (A ), known as amyloid plaques. Recent epidemiological studies suggest a link between statin intake, and a lowered incidence of AD. Statins are 3-hydroxy-3-methylglutaryl co-enzyme reductase (HMG) inhibitors, which are one of the most commonly prescribed drug groups used to lower serum cholesterol levels in patients with heart disease. Some of the pleiotropic effects of statins which are gaining attention are its ability to reduce A production and deposition, inhibit caspase-3 mediated apoptosis, and demonstrate anti-inflammatory properties by reducing interleukin-6 (IL-6) levels. The molecular mechanisms responsible for the pleiotropic effects of statins in promoting neuronal survival are not fully understood. Our own research has shown that statins promote anti-apoptotic responses against A -neurotoxicity through -catenin-TCF/LEF signaling however, other anti-apoptotic statin mediated signaling pathways may also be involved. This review will describe AD pathogenesis, A production, and the role of statins in mitigating these effects.

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Section: Anti-apoptotic Signaling Pathways Of Statins In Admentioning

confidence: 68%

Section: Anti-apoptotic Signaling Pathways Of Statins In Admentioning

confidence: 99%

See 1 more Smart Citation

Neuroprotective Role of Statins in Alzheimer`s Disease: Anti-Apoptotic Signaling~!2009-02-06~!2010-04-04~!2010-06-22~!

Hunt¹,

Salins²,

Anderson³

et al. 2010

TONEURJ

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show abstract

“…In all cases, the NG2 expression level has direct correlations with both β1 integrin activation and the level of PI3K phosphorylation [75] . (GSK-3β, an enzyme that phosphorylates β-catenin) [76] , leading to the degradation of β-catenin and inactivation of the Wnt signaling pathway [77] . The activation of Wnt signaling can reverse Aβ fibril-induced neurodegeneration and behavioral impairment [78,79] , while inhibition of the Wnt/β-catenin pathway prevents the differentiation of NG2 cells and other precursor cells [80,81] .…”

Section: On Glioma Cell Survivalmentioning

confidence: 99%

“…Therefore, although glial progenitor cells (GPCs) still exist in the brains of AD patients, they are unable to generate adequate numbers of new neurons to compensate for the neuronal loss caused by Aβ aggregation. If this mechanism really exists, reagents like PKC agonists or lovastatin (a reagent that may affect cholesterol synthesis and reduce Aβ production) can be used to defend against Aβ-induced neuronal damage [86,87] .…”

Section: Fatementioning

confidence: 99%

Roles of NG2 glial cells in diseases of the central nervous system

Zhao

2011

Neurosci. Bull.

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Activation of Wnt/β‐catenin signaling by lithium chloride attenuates d‐galactose‐induced neurodegeneration in the auditory cortex of a rat model of aging

et al. 2017

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Degeneration of the central auditory system, which is characterized by reduced understanding of speech and source localization of sounds, is an important cause of age‐related hearing loss (presbycusis). Accumulating evidence has demonstrated that Wnt/β‐catenin signaling plays an essential role in the development of the auditory system but its potential role in presbycusis remains unclear. In this study, we used a rat model of aging, created by chronic systemic exposure to d ‐galactose ( d ‐gal), and explored changes in Wnt/β‐catenin signaling in the auditory cortex. A decrease in Wnt/β‐catenin signaling in the auditory cortex was found in both naturally aging and d ‐gal‐mimetic aging rats, as indicated by increased GSK 3β activity and decreased β‐catenin activity. Moreover, lithium chloride (Licl), an activator of Wnt signaling pathway, was administered long term to 15‐month‐old d ‐gal‐treated rats. Activation of Wnt/β‐catenin signaling by Licl attenuated d ‐gal‐induced auditory cortex apoptosis and neurodegeneration. Bmi1, a transcription factor implicated in antiaging and resistance to apoptosis, can be modulated by β‐catenin activity. Here, we showed that the expression of Bmi1 was reduced and the expression of its downstream genes, p16 INK 4a , p19 Arf , and p53 were increased in the auditory cortex both of naturally aging and d ‐gal‐mimetic aging rats. In addition, Licl significantly increased Bmi1 expression and reduced p16 INK 4a , p19 Arf , and p53 expression. Our results indicated that decreased Wnt/β‐catenin signaling might participate in the pathogenesis of central presbycusis through modulating the expression of Bmi1. Wnt/β‐catenin signaling might be used as a potential therapeutic target against presbycusis.

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Lovastatin protects human neurons against Aβ-induced toxicity and causes activation of β-catenin–TCF/LEF signaling

Cited by 46 publications

References 22 publications

Neuroprotective Role of Statins in Alzheimer`s Disease: Anti-Apoptotic Signaling~!2009-02-06~!2010-04-04~!2010-06-22~!

Neuroprotective Role of Statins in Alzheimer`s Disease: Anti-Apoptotic Signaling~!2009-02-06~!2010-04-04~!2010-06-22~!

Roles of NG2 glial cells in diseases of the central nervous system

Activation of Wnt/β‐catenin signaling by lithium chloride attenuates d‐galactose‐induced neurodegeneration in the auditory cortex of a rat model of aging

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