CMS121, a fatty acid synthase inhibitor, protects against excess lipid peroxidation and inflammation and alleviates cognitive loss in a transgenic mouse model of Alzheimer's disease

Ates, Gamze; Goldberg, Joshua; Currais, António; Maher, Pamela

doi:10.1016/j.redox.2020.101648

Cited by 89 publications

(89 citation statements)

References 76 publications

(111 reference statements)

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“…Ates et al [ 171 ] showed in an animal model that inhibition of fatty acid synthase (FASN) by CMS121 decreased lipid peroxidation. CMS121 treatment reduced the levels of 15LOX2 in the hippocampus compared to those of untreated WT mice.…”

Section: Ferroptosis In Neurodegenerative Diseasesmentioning

confidence: 99%

Ferroptosis Mechanisms Involved in Neurodegenerative Diseases

Reichert

Freitas

Sampaio-Silva

et al. 2020

IJMS

274

148

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Ferroptosis is a type of cell death that was described less than a decade ago. It is caused by the excess of free intracellular iron that leads to lipid (hydro) peroxidation. Iron is essential as a redox metal in several physiological functions. The brain is one of the organs known to be affected by iron homeostatic balance disruption. Since the 1960s, increased concentration of iron in the central nervous system has been associated with oxidative stress, oxidation of proteins and lipids, and cell death. Here, we review the main mechanisms involved in the process of ferroptosis such as lipid peroxidation, glutathione peroxidase 4 enzyme activity, and iron metabolism. Moreover, the association of ferroptosis with the pathophysiology of some neurodegenerative diseases, namely Alzheimer’s, Parkinson’s, and Huntington’s diseases, has also been addressed.

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Section: Ferroptosis In Neurodegenerative Diseasesmentioning

confidence: 99%

Ferroptosis Mechanisms Involved in Neurodegenerative Diseases

Reichert

Freitas

Sampaio-Silva

et al. 2020

IJMS

274

148

View full text Add to dashboard Cite

show abstract

“…Sphk2, another neuronal sphingosine kinase, also have been reported to protect against hippocampal volume loss and demyelination in male J20 mice ( Lei et al, 2019 ). Additionally, a fatty acid synthase inhibitor, CMS121, protects against ferroptosis-induced lipid peroxidation and alleviates cognitive impairment in APP/PS1-transgenic mice ( Ates et al, 2020 ). Taken together, these findings demonstrated that restoration of lipid peroxidation effectively rescued the AD-like symptoms and lipid metabolism pathway will be a potential therapeutic target for the prevention of this disease in the future.…”

Section: Ferroptosis-related Signaling Pathways In Admentioning

confidence: 99%

Ferroptosis, a Potential Therapeutic Target in Alzheimer’s Disease

Chen

Jiang

et al. 2021

Front. Cell Dev. Biol.

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Cell death is a common phenomenon in the progression of Alzheimer’s disease (AD). However, the mechanism of triggering the death of neuronal cells remains unclear. Ferroptosis is an iron-dependent lipid peroxidation-driven cell death and emerging evidences have demonstrated the involvement of ferroptosis in the pathological process of AD. Moreover, several hallmarks of AD pathogenesis were consistent with the characteristics of ferroptosis, such as excess iron accumulation, elevated lipid peroxides, and reactive oxygen species (ROS), reduced glutathione (GSH), and glutathione peroxidase 4 (GPX4) levels. Besides, some ferroptosis inhibitors can relieve AD-related pathological symptoms in AD mice and exhibit potential clinical benefits in AD patients. Therefore, ferroptosis is gradually being considered as a distinct cell death mechanism in the pathogenesis of AD. However, direct evidence is still lacking. In this review, we summarize the features of ferroptosis in AD, its underlying mechanisms in AD pathology, and review the application of ferroptosis inhibitors in both AD clinical trials and mice/cell models, to provide valuable information for future treatment and prevention of this devastating disease.

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“…In a very recent paper by Ates et al [ 82 ], promising results were obtained using a fisetin derivative. The substance, CMS121, is a small molecule derived from fisetin, which is developed by a drug discovery paradigm based on phenotypic screening assays.…”

Section: Fisetinmentioning

confidence: 99%

Nutraceutical Approaches of Autophagy and Neuroinflammation in Alzheimer’s Disease: A Systematic Review

et al. 2020

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Aging and the emergence of age-associated illnesses are one of the major challenges of our present society. Alzheimer’s disease (AD) is closely associated with aging and is defined by increasing memory loss and severe dementia. Currently, there are no therapy options available that halt AD progression. This work investigates three hallmarks of the disease (autophagy, neuroinflammation, and senescence) and systematically analyzes if there is a beneficial effect from three substances derived from food sources, the so called “nutraceuticals” epigallocatechin gallate, fisetin, and spermidine, on these hallmarks. The results imply a positive outlook for the reviewed substances to qualify as a novel treatment option for AD. A combination of nutraceutical substances and other preventive measures could have significant clinical impact in a multi-layered therapy approach to counter AD.

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CMS121, a fatty acid synthase inhibitor, protects against excess lipid peroxidation and inflammation and alleviates cognitive loss in a transgenic mouse model of Alzheimer's disease

Cited by 89 publications

References 76 publications

Ferroptosis Mechanisms Involved in Neurodegenerative Diseases

Ferroptosis Mechanisms Involved in Neurodegenerative Diseases

Ferroptosis, a Potential Therapeutic Target in Alzheimer’s Disease

Nutraceutical Approaches of Autophagy and Neuroinflammation in Alzheimer’s Disease: A Systematic Review

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