The neuroprotective effect of simvastatin on the cerebellum of experimentally-induced diabetic rats through klotho upregulation: An immunohistochemical study

Youssef, Ola Mohammed; Morsy, Amira Ibrahim; El-Shahat, Mona A.; Shams, Amany; Abd-Elhady, Samira Lotfy

doi:10.1016/j.jchemneu.2020.101803

Cited by 9 publications

(3 citation statements)

References 43 publications

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“…Youssef и соавт. [73], посвящённая изучению экспрессии белка Klotho в мозжечке крыс с сахарным диабетом и нейропротекторного действия симвастатина. У исследуемых крыс выявлено снижение экспрессии белка Klotho и увеличение уровня каспазы-3.…”

Section: модуляция активности белка клото -новый терапевтический подх...unclassified

Klotho protein and atherosclerotic cardiovascular diseases: prolonging the thread of life

Alieva

Reznik

Teplova

et al. 2022

Medical Journal of the Russian Federation

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To date, the most widely used biomarkers are natriuretic peptides and cardiac troponins. Many other biomarkers have also been identified, but only a few of them have found application in actual clinical practice. This review focuses on the Klotho protein and its role in cardiovascular diseases. In 1997, a gene that slows down the aging process was identified. It was named Klotho (Greek, ώ, spinning; Latin, Clotho; English, Klotho) in honor of the goddess of ancient Greek mythology, spinning the thread of life and being the personification of the steady, calm course of fate. Mice with an insertional mutation in the region of the Klotho gene promoter were characterized by premature aging processes. Three families of Klotho are known: -Klotho, -Klotho, and -Klotho, and the most studied is -Klotho. The Klotho protein consists of a large extracellular domain and a short C-terminal intracellular region. The extracellular domain consists of two repeat sequences called KL1 and KL2. -Klotho and -Klotho contain the KL1 and KL2 domains, respectively, and -Klotho contains only the KL1 domain. The Klotho gene in humans is located on chromosome 13q12 and consists of five exons. The Klotho protein is mainly expressed in the distal convoluted tubules of the kidneys and the vascular epithelial plexus of the cerebral ventricles. At lower concentrations, the Klotho gene is also found in other organs and tissues, particularly in the heart. Many studies have demonstrated the protective role of the Klotho protein in cardiovascular pathology. The pleiotropic properties of this protein are reflected in the diversity and interaction of cardioprotective mechanisms. The regulation of the concentrations of the Klotho protein in the blood and its expression in heart cells with the help of drugs can play a significant role in cellular metabolism and represent a promising target for the treatment of heart and vascular pathologies.

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Section: модуляция активности белка клото -новый терапевтический подх...unclassified

Klotho protein and atherosclerotic cardiovascular diseases: prolonging the thread of life

Alieva

Reznik

Teplova

et al. 2022

Medical Journal of the Russian Federation

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“…The direct injection or convection-enhanced delivery approaches can bypass the BBB, but they are invasive and require surgical intervention, and the infiltration of agents into the parenchyma may be limited by diffusion . Hyperosmotic solutions via altering paracellular transport may be helpful for treating large volumes of diseased brain tissue, but the use of such reagents can lead to structural alterations to neurons due to the osmotic shrinkage. , Other strategies such as intranasal delivery and carrier protein-mediated transport suffer from nontargeted delivery or nontherapeutically relevant concentrations of drug delivery. , …”

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confidence: 99%

“…3 Hyperosmotic solutions via altering paracellular transport may be helpful for treating large volumes of diseased brain tissue, but the use of such reagents can lead to structural alterations to neurons due to the osmotic shrinkage. 4,5 Other strategies such as intranasal delivery and carrier proteinmediated transport suffer from nontargeted delivery or nontherapeutically relevant concentrations of drug delivery. 6 Focused ultrasound (FUS) combined with microbubbles (MBs) has been proven to be a promising approach to open the BBB for delivering drugs into the brain.…”

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confidence: 99%

Early Detection and Reversal of Cell Apoptosis Induced by Focused Ultrasound-Mediated Blood–Brain Barrier Opening

et al. 2021

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Focused ultrasound (FUS) combined with microbubbles (MBs) has recently emerged as a potential approach to open the blood–brain barrier (BBB) for delivering drugs into the brain. However, appropriate approaches are still lacking to monitor the sublethal damage during FUS-mediated BBB opening in vivo, especially the early stage cell apoptotic events. Here, we developed a kind of nanoprobe-loaded MBs (AV-ICG-NPs@MBs) which can monitor the apoptotic cells that occur during FUS-mediated BBB opening through encapsulating the annexin V-targeted nanoprobes AV-ICG-NPs into the cavity of lipid-PLGA hybrid MBs. When irradiated by FUS, AV-ICG-NPs@MBs in the cerebral blood vessels would produce cavitation, favoring the BBB opening. Meanwhile, AV-ICG-NPs@MBs would be destroyed and release their AV-ICG-NPs payload. These released AV-ICG-NPs can be further delivered into the brain via the destructed BBB and bind with the phosphatidylserine externalized on the membrane of apoptotic cells if this occurs, leading to the prolonged detention of fluorescent signals in the brain. Furthermore, we also provided an effective strategy to inhibit or reverse the possible damage to the brain from a FUS-mediated BBB opening technology, through developing AV-ICG-NPs/GAS@MBs that encapsulate the antioxidant gastrodin (GAS) into AV-ICG-NPs@MBs. Accompanied by FUS irradiation and bubble cavitation, GAS was released and delivered into the brain, where they scavenged the oxygen free radicals produced from cavitation, leading to significantly lower fluorescence signals in the brain due to the absence of externalized phosphatidylserine. In conclusion, our study provides an approach to monitor and inhibit cell apoptotic events during FUS-mediated BBB opening.

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Comorbidity of osteoporosis and Alzheimer’s disease: Is `AKT `-ing on cellular glucose uptake the missing link?

Fehsel

Christl

2022

Ageing Research Reviews

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The neuroprotective effect of simvastatin on the cerebellum of experimentally-induced diabetic rats through klotho upregulation: An immunohistochemical study

Cited by 9 publications

References 43 publications

Klotho protein and atherosclerotic cardiovascular diseases: prolonging the thread of life

Klotho protein and atherosclerotic cardiovascular diseases: prolonging the thread of life

Early Detection and Reversal of Cell Apoptosis Induced by Focused Ultrasound-Mediated Blood–Brain Barrier Opening

Comorbidity of osteoporosis and Alzheimer’s disease: Is `AKT `-ing on cellular glucose uptake the missing link?

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