CD36 – A novel molecular target in the neurovascular unit

Ioghen, Octavian Costin; Chițoiu, Leona; Gherghiceanu, Mihaela; Ceafalan, Laura Cristina; Hinescu, Mihail Eugen

doi:10.1111/ejn.15147

Cited by 18 publications

(12 citation statements)

References 83 publications

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“…Therefore, the BBB SR-B is only an endocytosis system, and does not mediate transcytosis through the BBB [506]. The microvascular SR-B/CD36 is believed to participate in phagocytosis at the neurovascular unit [829]. The presence of PS80, or other surfactants, in the PNP formulation is essential for BBB transport [830].…”

Section: Polymeric Nanoparticlesmentioning

confidence: 99%

A Historical Review of Brain Drug Delivery

Pardridge

2022

Pharmaceutics

106

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The history of brain drug delivery is reviewed beginning with the first demonstration, in 1914, that a drug for syphilis, salvarsan, did not enter the brain, due to the presence of a blood–brain barrier (BBB). Owing to restricted transport across the BBB, FDA-approved drugs for the CNS have been generally limited to lipid-soluble small molecules. Drugs that do not cross the BBB can be re-engineered for transport on endogenous BBB carrier-mediated transport and receptor-mediated transport systems, which were identified during the 1970s–1980s. By the 1990s, a multitude of brain drug delivery technologies emerged, including trans-cranial delivery, CSF delivery, BBB disruption, lipid carriers, prodrugs, stem cells, exosomes, nanoparticles, gene therapy, and biologics. The advantages and limitations of each of these brain drug delivery technologies are critically reviewed.

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Section: Polymeric Nanoparticlesmentioning

confidence: 99%

A Historical Review of Brain Drug Delivery

Pardridge

2022

Pharmaceutics

106

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“…For example, CD36 has been linked to cardiovascular diseases including stroke or chronic ischemia 42 , 66 and cerebral microhemorrhages caused by ministrokes could contribute to the development of a DAT 67 , thus potentially mediating the effect of CD36 polymorphisms on AD. Taken together, there are diverse mechanisms, potentially involved in the etiology of AD, where CD36 has a role (recent reviews 42 , 68 , 69 ). Results of very recent animal studies expand this diversity by demonstrating CD36 involvement in an AD-associated blood brain barrier disruption 70 , and in an interaction with the nerve growth regulator1 (NEGR1) 71 , i.e., in AD-related mechanisms distinct from those active in the amyloid/tau pathways and/or the amyloid-β phagocytosis by microglia.…”

Section: Discussionmentioning

confidence: 99%

Six genetically linked mutations in the CD36 gene significantly delay the onset of Alzheimer's disease

Šerý

Zeman

Sheardová

et al. 2022

Sci Rep

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The risk of Alzheimer’s disease (AD) has a strong genetic component, also in the case of late-onset AD (LOAD). Attempts to sequence whole genome in large populations of subjects have identified only a few mutations common to most of the patients with AD. Targeting smaller well-characterized groups of subjects where specific genetic variations in selected genes could be related to precisely defined psychological traits typical of dementia is needed to better understand the heritability of AD. More than one thousand participants, categorized according to cognitive deficits, were assessed using 14 psychometric tests evaluating performance in five cognitive domains (attention/working memory, memory, language, executive functions, visuospatial functions). CD36 was selected as a gene previously shown to be implicated in the etiology of AD. A total of 174 polymorphisms were tested for associations with cognition-related traits and other AD-relevant data using the next generation sequencing. Several associations between single nucleotide polymorphisms (SNP’s) and the cognitive deficits have been found (rs12667404 with language performance, rs3211827 and rs41272372 with executive functions, rs137984792 with visuospatial performance). The most prominent association was found between a group of genotypes in six genetically linked and the age at which the AD patients presented with, or developed, a full-blown dementia. The identified alleles appear to be associated with a delay in the onset of LOAD. In silico studies suggested that the SNP’s alter the expression of CD36 thus potentially affecting CD36-related neuroinflammation and other molecular and cellular mechanisms known to be involved in the neuronal loss leading to AD. The main outcome of the study is an identification of a set of six new mutations apparently conferring a distinct protection against AD and delaying the onset by about 8 years. Additional mutations in CD36 associated with certain traits characteristic of the cognitive decline in AD have also been found.

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“…While simple diffusion has been posited as a mechanism for FA uptake [ 18 ], our data contributed to the growing evidence that uptake of long-chain FA is primarily mediated by protein transporters [ 20 ]. CD36 is widely expressed in many types of cells including hepatocytes, adipocytes, microvascular endothelial cells, cardiomyocytes, astrocytes, microglia, and neurons [ 37 , 38 , 39 ]. In this study, we used BODIPY TM FL C12 to examine FA uptake for several reasons.…”

Section: Discussionmentioning

confidence: 99%

Role of CD36 in Palmitic Acid Lipotoxicity in Neuro-2a Neuroblastoma Cells

Urso

Zhou

2021

Biomolecules

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Elevated level of palmitic acid (PA), a long-chain saturated fatty acid (SFA), is lipotoxic to many different types of cells including Neuro-2a (N2a) neuroblastoma cells. CD36 is a multifunctional membrane glycoprotein that acts as a fatty acid translocase (FAT) facilitating the transport of long-chain free fatty acids (FFAs) into cells, serves a fatty acid (FA) sensing function in areas including taste buds and the proximal gut, and acts as a scavenger receptor that binds to many ligands, including FAs, collagen, oxidized low-density lipoproteins, and anionic phospholipids. However, the involvement of CD36 in FA uptake and PA lipotoxicity in N2a cells remains unclear. In this study, we examined FA uptake in BSA- and PA-treated N2a cells and investigated the involvement of CD36 in FA uptake and PA lipotoxicity in N2a cells. Our data showed that PA treatment promoted FA uptake in N2a cells, and that treatment with sulfo-N-succinimidyl oleate (SSO), a CD36 inhibitor, significantly decreased FA uptake in BSA- and PA-treated N2a cells, and ameliorated PA-induced decrease of cell viability, decrease of diploid cells, and increase of tetraploid cells. We also found that CD36 knockdown significantly decreased FA uptake in both BSA- and PA-treated cells as compared to their corresponding wild-type controls, and dramatically attenuated PA-induced cell cycle defects in N2a cells. Our data suggest that CD36 may play a critical role in FA uptake and PA lipotoxicity in N2a cells. CD36 may therefore represent a regulatory target against pathologies caused by excess FAs.

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CD36 – A novel molecular target in the neurovascular unit

Cited by 18 publications

References 83 publications

A Historical Review of Brain Drug Delivery

A Historical Review of Brain Drug Delivery

Six genetically linked mutations in the CD36 gene significantly delay the onset of Alzheimer's disease

Role of CD36 in Palmitic Acid Lipotoxicity in Neuro-2a Neuroblastoma Cells

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