Statins and autoimmunity: State-of-the-art

Dehnavi, Sajad; Sohrabi, Nasrin; Sadeghi, Mahvash; Lansberg, Peter; Banach, Maciej; Al-Rasadi, Khalid; Johnston, Thomas P.; Sahebkar, Amirhossein

doi:10.1016/j.pharmthera.2020.107614

Cited by 44 publications

(32 citation statements)

References 157 publications

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“…During the last 40 years, statins have revolutionized the prevention of atherosclerotic coronary artery disorders. Lovastatin, the first statin family member, was introduced as a drug agent to decrease low-density lipoprotein cholesterol [25]. Statins are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors that have a similar structure to 3-hydroxy-3-methylglutaryl-coenzyme A and inhibit the L-mevalonate synthesis and subsequently decrease the hepatocellular cholesterol production [26][27][28].…”

Section: Statinsmentioning

confidence: 99%

Targeting AMPK by Statins: A Potential Therapeutic Approach

Dehnavi

Kiani

Sadeghi

et al. 2021

Drugs

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Statins are a group of lipid-lowering drugs that inhibit cholesterol biosynthesis and have anti-inflammatory, anti-tumor, and immunomodulatory properties. Several lines of evidence indicate that statins regulate multiple proteins associated with the regulation of differing cellular pathways. The 5′-adenosine monophosphate-activated protein kinase (AMPK) pathway plays an important role in metabolism homeostasis with effects on cellular processes including apoptosis and the inflammatory responses through several pathways. Recently, it has been shown that statins can affect the AMPK pathway in differing physiological and pathological ways, resulting in anti-cancer, cardio-protective, neuro-protective, and anti-tubercular effects; additionally, they have therapeutic effects on non-alcoholic fatty liver disease and diabetes mellitus-associated complications. Statins activate AMPK as an energy sensor that inhibits cell proliferation and induces apoptosis in cancer cells, whilst exerting its cardio-protective effects through inhibition of inflammation and fibrosis, and promotion of angiogenesis. Furthermore, statin-associated AMPK activation leads to decreased lipid accumulation and decreased amyloid beta deposition in the liver and brain, respectively, and may have therapeutic effects on the liver and neurons. In this review, we summarize the results of studies of AMPK-associated therapeutic effects of statins in different pathological conditions.

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Section: Statinsmentioning

confidence: 99%

Targeting AMPK by Statins: A Potential Therapeutic Approach

Dehnavi

Kiani

Sadeghi

et al. 2021

Drugs

Self Cite

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“…In clinical treatment of various diseases ranging from cancer to auto-immune diseases and infection, statins (i.e., lovastatin or simvastatin) are routinely applied as inhibitors of cholesterol biosynthesis. Statin application affects both cholesterol levels in cellular membranes as well as in the blood stream and consequently affects cellular mechanisms and signaling pathways relying on membrane compartmentalization [ 215 , 216 ].…”

Section: Alterations In the Lipid Composition Of Membranes—opportunities For Clinical Exploitationmentioning

confidence: 99%

Regulation of Death Receptor Signaling by S-Palmitoylation and Detergent-Resistant Membrane Micro Domains—Greasing the Gears of Extrinsic Cell Death Induction, Survival, and Inflammation

Fritsch

Särchen

Schneider-Brachert

2021

Cancers

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Death-receptor-mediated signaling results in either cell death or survival. Such opposite signaling cascades emanate from receptor-associated signaling complexes, which are often formed in different subcellular locations. The proteins involved are frequently post-translationally modified (PTM) by ubiquitination, phosphorylation, or glycosylation to allow proper spatio-temporal regulation/recruitment of these signaling complexes in a defined cellular compartment. During the last couple of years, increasing attention has been paid to the reversible cysteine-centered PTM S-palmitoylation. This PTM regulates the hydrophobicity of soluble and membrane proteins and modulates protein:protein interaction and their interaction with distinct membrane micro-domains (i.e., lipid rafts). We conclude with which functional and mechanistic roles for S-palmitoylation as well as different forms of membrane micro-domains in death-receptor-mediated signal transduction were unraveled in the last two decades.

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“…50 Statins can also activate anti-inflammatory transcription factor-peroxisome proliferator-activated receptors (PPARs), interfering with NFκB activity. 51…”

mentioning

confidence: 99%

Rosuvastatin Nanomicelles Target Neuroinflammation and Improve Neurological Deficit in a Mouse Model of Intracerebral Hemorrhage

Zhou

et al. 2021

IJN

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Background: Intracerebral hemorrhage (ICH), a devastating subtype of stroke, has a poor prognosis. However, there is no effective therapy currently available due to its complex pathological progression, in which neuroinflammation plays a pivotal role in secondary brain injury. In this work, the use of statin-loaded nanomicelles to target the neuroinflammation and improve the efficacy was studied in a mouse model of ICH. Methods: Rosuvastatin-loaded nanomicelles were prepared by a co-solvent evaporation method using polyethylene glycol-poly(ε-caprolactone) (PEG-PCL) copolymer as a carrier. The prepared nanomicelles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS), and then in vitro and in vivo studies were performed. Results: TEM shows that the nanomicelles are spherical with a diameter of about 19.41 nm, and DLS shows that the size, zeta potential, and polymer dispersity index of the nanomicelles were 23.37 nm, −19.2 mV, and 0.221, respectively. The drug loading content is 8.28%. The in vivo study showed that the nanomicelles significantly reduced neuron degeneration, inhibited the inflammatory cell infiltration, reduced the brain edema, and improved neurological deficit. Furthermore, it was observed that the nanomicelles promoted the polarization of microglia/macrophages to M2 phenotype, and also the expression of the proinflammatory cytokines, such as IL-1β and TNF-α, was significantly down-regulated, while the expression of the anti-inflammatory cytokine IL-10 was significantly up-regulated. The related mechanism was proposed and discussed. Conclusion:The nanomicelles treatment suppressed the neuroinflammation that might contribute to the promoted nerve functional recovery of the ICH mouse, making it potential to be applied in clinic.

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Statins and autoimmunity: State-of-the-art

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Cited by 44 publications

References 157 publications

Targeting AMPK by Statins: A Potential Therapeutic Approach

Targeting AMPK by Statins: A Potential Therapeutic Approach

Regulation of Death Receptor Signaling by S-Palmitoylation and Detergent-Resistant Membrane Micro Domains—Greasing the Gears of Extrinsic Cell Death Induction, Survival, and Inflammation

Rosuvastatin Nanomicelles Target Neuroinflammation and Improve Neurological Deficit in a Mouse Model of Intracerebral Hemorrhage

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