Regulation of ABCG4 transporter expression by sterols and LXR ligands

Yang, Alryel; Alrosan, Amjad Z.; Sharpe, Laura J.; Brown, Andrew; Callaghan, Richard; Gelissen, Ingrid C.

doi:10.1016/j.bbagen.2020.129769

Cited by 8 publications

(7 citation statements)

References 38 publications

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“…Most likely, oxysterols block cholesterol synthesis by inhibiting the transport of SREBPs from the ER to the Golgi apparatus; in particular, they act by binding to insulin-induced gene proteins (Insig), favoring their binding to the SREBP-escort protein Scap [ 136 ]. Moreover, the oxysterols 24-OHC, 27-OHC and 25-OHC are able to induce the expression of ABCA1 and ABCG1 transporters in U-87 MG astrocytoma cells; among the three oxysterols, 24-OHC was found to be the most potent [ 137 ].…”

Section: The Involvement Of Astrocytes In Brain Cholesterol Dysmetabolismmentioning

confidence: 99%

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Cholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?

Staurenghi¹,

Giannelli²,

Testa³

et al. 2021

Antioxidants

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In recent decades, the impairment of cholesterol metabolism in the pathogenesis of Alzheimer’s disease (AD) has been intensively investigated, and it has been recognized to affect amyloid β (Aβ) production and clearance, tau phosphorylation, neuroinflammation and degeneration. In particular, the key role of cholesterol oxidation products, named oxysterols, has emerged. Brain cholesterol metabolism is independent from that of peripheral tissues and it must be preserved in order to guarantee cerebral functions. Among the cells that help maintain brain cholesterol homeostasis, astrocytes play a starring role since they deliver de novo synthesized cholesterol to neurons. In addition, other physiological roles of astrocytes are to modulate synaptic transmission and plasticity and support neurons providing energy. In the AD brain, astrocytes undergo significant morphological and functional changes that contribute to AD onset and development. However, the extent of this contribution and the role played by oxysterols are still unclear. Here we review the current understanding of the physiological role exerted by astrocytes in the brain and their contribution to AD pathogenesis. In particular, we focus on the impact of cholesterol dysmetabolism on astrocyte functions suggesting new potential approaches to develop therapeutic strategies aimed at counteracting AD development.

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Section: The Involvement Of Astrocytes In Brain Cholesterol Dysmetabolismmentioning

confidence: 99%

“…10, x FOR PEER REVIEW 9 of 23OHC, 27-OHC and 25-OHC are able to induce the expression of ABCA1 and ABCG1 transporters in U-87 MG astrocytoma cells; among the three oxysterols, 24-OHC was found to be the most potent[137].…”

mentioning

confidence: 98%

Cholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?

Staurenghi¹,

Giannelli²,

Testa³

et al. 2021

Antioxidants

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“…As well, LXRs contribute to the regulation of brain cholesterol metabolism [ 19 ]. LXRs knockout mice develop neurodegeneration due to cholesterol-induced synaptic dysfunction and neuronal loss [ 35 ]. Of interest, adiponectin attenuates the development of neurodegeneration through the activation of LXRs [ 36 ].…”

Section: Liver X Receptormentioning

confidence: 99%

Role of Brain Liver X Receptor in Parkinson’s Disease: Hidden Treasure and Emerging Opportunities

Alnaaim,

Al-Kuraishy,

Alexiou

et al. 2023

Mol Neurobiol

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Parkinson’s disease (PD) is a neurodegenerative disease due to the degeneration of dopaminergic neurons (DNs) in the substantia nigra (SN). The liver X receptor (LXR) is involved in different neurodegenerative diseases. Therefore, the objective of the present review was to clarify the possible role of LXR in PD neuropathology. LXRs are the most common nuclear receptors of transcription factors that regulate cholesterol metabolism and have pleiotropic effects, including anti-inflammatory effects and reducing intracellular cholesterol accumulation. LXRs are highly expressed in the adult brain and act as endogenous sensors for intracellular cholesterol. LXRs have neuroprotective effects against the development of neuroinflammation in different neurodegenerative diseases by inhibiting the expression of pro-inflammatory cytokines. LXRs play an essential role in mitigating PD neuropathology by reducing the expression of inflammatory signaling pathways, neuroinflammation, oxidative stress, mitochondrial dysfunction, and enhancement of BDNF signaling.In conclusion, LXRs, through regulating brain cholesterol homeostasis, may be effectual in PD. Also, inhibition of node-like receptor pyrin 3 (NLRP3) inflammasome and nuclear factor kappa B (NF-κB) by LXRs could effectively prevent neuroinflammation in PD. Taken together, LXRs play a crucial role in PD neuropathology by inhibiting neuroinflammation and associated degeneration of DNs.

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“…Cholesterol, cholesterol synthesis intermediates (desmosterol, lathosterol, lanosterol), oxysterols [120,[125][126][127] Note that the substrates listed here are not limited to the brain and may reflect data from systemic studies since investigations regarding the cholesterol/lipid-transporting activity of ABC transporters within the brain are still limited. "•" denotes expression has been observed in the cell line, "-" indicates no expression or no data.…”

Section: Transport Of Brain Cholesterol By Abc Transportersmentioning

confidence: 99%

Balancing cholesterol in the brain: from synthesis to disposal

Qian

Chai

Gelissen

et al. 2022

Explor Neuroprot Ther

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The cholesterol is a vital component of cell membranes and myelin sheaths, and a precursor for essential molecules such as steroid hormones. In humans, cholesterol is partially obtained through the diet, while the majority is synthesized in the body, primarily in the liver. However, the limited exchange between the central nervous system and peripheral circulation, due to the presence of the blood-brain barrier, necessitates cholesterol in the brain to be exclusively acquired from local de novo synthesis. This cholesterol is reutilized efficiently, rendering a much slower overall turnover of the compound in the brain as compared with the periphery. Furthermore, brain cholesterol is regulated independently from peripheral cholesterol. Numerous enzymes, proteins, and other factors are involved in cholesterol synthesis and metabolism in the brain. Understanding the unique mechanisms and pathways involved in the maintenance of cholesterol homeostasis in the brain is critical, considering perturbations to these processes are implicated in numerous neurodegenerative diseases. This review focuses on the developing understanding of cholesterol metabolism in the brain, discussing the sites and processes involved in its synthesis and regulation, as well as the mechanisms involved in its distribution throughout, and elimination from, the brain.

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Regulation of ABCG4 transporter expression by sterols and LXR ligands

Cited by 8 publications

References 38 publications

Cholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?

Cholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?

Role of Brain Liver X Receptor in Parkinson’s Disease: Hidden Treasure and Emerging Opportunities

Balancing cholesterol in the brain: from synthesis to disposal

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