RETRACTED: The oxysterol 27‐hydroxycholesterol regulates α‐synuclein and tyrosine hydroxylase expression levels in human neuroblastoma cells through modulation of liver X receptors and estrogen receptors–relevance to Parkinson’s disease

Marwarha, Gurdeep; Rhen, Turk; Schommer, Trevor; Ghribi, Othman

doi:10.1111/j.1471-4159.2011.07497.x

Cited by 77 publications

(53 citation statements)

References 105 publications

(196 reference statements)

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“…In SH-SY5Y cells, 24-hydroxycholesterol and 27-hydroxycholesterol, which are ligands for LXR, have differential effects on tyrosine hydroxylase and α-synuclein: 24-hydroxycholesterol increases the levels of tyrosine hydroxylase, whereas 27-hydroxycholesterol increases the levels of α-synuclein (37). 27-Hydroxycholesterol activates LXRβ and induces its binding to LXRE in the α-synuclein promoter, up-regulating α-synuclein expression in SH-SY5Y cells (33,38). In these in vitro studies, LXRβ was expressed in neuroblastoma cells.…”

Section: Discussionmentioning

confidence: 87%

Liver X receptor β protects dopaminergic neurons in a mouse model of Parkinson disease

Dai

Tan

et al. 2012

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

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Parkinson disease (PD) is a progressive neurodegenerative disease whose progression may be slowed, but at present there is no pharmacological intervention that would stop or reverse the disease. Liver X receptor β (LXRβ) is a member of the nuclear receptor super gene family expressed in the central nervous system, where it is important for cortical layering during development and survival of dopaminergic neurons throughout life. In the present study we have used the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD to investigate the possible use of LXRβ as a target for prevention or treatment of PD. The dopaminergic neurons of the substantia nigra of LXRβ −/− mice were much more severely affected by MPTP than were those of their WT littermates. In addition, the number of activated microglia and GFAPpositive astrocytes was higher in the substantia nigra of LXRβ −/− mice than in WT littermates. Administration of the LXR agonist GW3965 to MPTP-treated WT mice protected against loss of dopaminergic neurons and of dopaminergic fibers projecting to the striatum, and resulted in fewer activated microglia and astroglia. Surprisingly, LXRβ was not expressed in the neurons of the substantia nigra but in the microglia and astroglia. We conclude that LXR agonists may have beneficial effects in treatment of PD by modulating the cytotoxic functions of microglia.midbrain | neurodegeneration | neuroinflammation P arkinson disease (PD) is a common neurodegenerative disorder whose clinical features include tremor, slowness of movement, stiffness, and postural instability (1). PD is characterized by microgliosis, astrogliosis, progressive degeneration of dopaminergic neurons, presence of Lewy bodies in dopaminergic neurons, and α-synuclein accumulation in substantia nigra pars compacta (2). Although there are drugs that alleviate symptoms of PD, chronic use of these drugs results in debilitating side effects (3), and none seems to halt the progression of the disease. The etiology of PD remains unknown, but environmental toxins, genetic factors, and mitochondrial dysfunction are thought to be involved. Neuroinflammation (microglial activation, astrogliosis, and lymphocyte infiltration) results in production of cytotoxic molecules (4-9) that are directly involved in neuronal degeneration. It is now recognized that targeting neuroinflammation is one intervention that can slow down the progression of PD (10).1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that targets rather specifically dopaminergic neurons that are involved in PD; its administration leads to severe and irreversible PD-like syndrome in humans and nonhuman primates, with most of the biochemical and pathological hallmarks of PD (11), i.e., marked loss of dopaminergic neurons, astrogliosis, and activated microglia in the substantia nigra pars compacta (12). In 2002, Wu et al. (13) showed that dopaminergic neurons in the substantia nigra could be protected from MPTP-induced damage by the tetracycline derivative minocycline. This capaci...

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Section: Discussionmentioning

confidence: 87%

Liver X receptor β protects dopaminergic neurons in a mouse model of Parkinson disease

Dai

Tan

et al. 2012

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

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“…Overall, we show that 27-OHC and the synthetic LXR agonist GW3965 increase the binding of LXRβ, not LXRα, to the α-synuclein promoter (Marwarha et al, 2011). This may be primarily attributed to the fact that α-synuclein is an LXRβ-regulated gene rather than LXRβ being more abundantly expressed in SH-SY5Y cells.…”

Section: Introductionmentioning

confidence: 79%

Does the oxysterol 27-hydroxycholesterol underlie Alzheimer's disease–Parkinson's disease overlap?

Marwarha

Ghribi

2015

Experimental Gerontology

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Alzheimer’s disease (AD), the most common form of dementia, is characterized histopathologically by the deposition of β-amyloid (Aβ) plaques and neurofibrillary tangles-containing hyperphosphorylated tau protein in the brain. Parkinson’s disease (PD), the most common movement disorder, is characterized by the aggregation of α-synuclein protein in Lewy body inclusions and the death of dopaminergic neurons in the substantia nigra. Based on their pathological signatures, AD and PD can be considered as two different disease entities. However, a subpopulation of PD patients also exhibit Aβ plaques, and AD patients exhibit α-synuclein aggregates. This overlap between PD and AD suggests that common pathological pathways exist for the two diseases. Identification of factors and cellular mechanisms by which these factors can trigger pathological hallmarks for AD/PD overlap may help in designing disease-modifying therapies that can reverse or stop the progression of AD and PD. For the last decade, work in our laboratory has shown that fluctuations in the levels of cholesterol oxidation products (oxysterols) may correlate with the onset of AD and PD. In this review, we will provide results from our laboratory and data from literature that converge to strongly suggest the involvement of cholesterol and cholesterol oxidation products in the pathogenesis of AD and PD. We will specifically delineate the role of and the underlying mechanisms by which increased levels of the oxysterol 27-hydroxycholesterol contribute to the pathogenesis of AD, PD, and AD/PD overlap.

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“…α-Synuclein contains two cholesterol-binding domains [3], and one study on cell culture found that α-synuclein aggregation could be induced by cholesterol and reduced by lipid-lowering medicines such as statins [4]. Moreover, the cholesterol derivative-27-hydroxycholesterol was suggested to increase the level of α-synuclein and reduces dopamine synthesis [5]. Therefore, lipids, especially cholesterol, may play a role in the pathogenesis of PD.…”

Section: Introductionmentioning

confidence: 99%

The serum lipid profile of Parkinson's disease patients: a study from China

Guo

Song

Chen

et al. 2014

International Journal of Neuroscience

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RETRACTED: The oxysterol 27‐hydroxycholesterol regulates α‐synuclein and tyrosine hydroxylase expression levels in human neuroblastoma cells through modulation of liver X receptors and estrogen receptors–relevance to Parkinson’s disease

Cited by 77 publications

References 105 publications

Liver X receptor β protects dopaminergic neurons in a mouse model of Parkinson disease

Liver X receptor β protects dopaminergic neurons in a mouse model of Parkinson disease

Does the oxysterol 27-hydroxycholesterol underlie Alzheimer's disease–Parkinson's disease overlap?

The serum lipid profile of Parkinson's disease patients: a study from China

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