Apolipoprotein J in Alzheimer’s Disease: Shedding Light on Its Role with Cell Signaling Pathway Perspective and Possible Therapeutic Approaches

Moezzi, Seyed Mohammad Iman; Mozafari, Negin; Fazel-Hoseini, Seyed-Mostafa; Nadimi-Parashkoohi, Sadra; Abbasi, Hosein; Ashrafi, Hajar; Azadi, Amir

doi:10.1021/acschemneuro.0c00637

Cited by 10 publications

(9 citation statements)

References 90 publications

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“…Clusterin, also known as Apolipoprotein J, is a well-conserved, 50 kDa heterodimer protein [159]. It is mainly synthesized in the liver, prostate, and ovaries from where it is secreted into the plasma [160,161].…”

Section: Clusterinmentioning

confidence: 99%

“…The concentration of circulating clusterin in human plasma is ~100 µg/mL, while it is present at only ~2 µg/mL in the CSF [162,163]. Clusterin is primarily expressed and released from astrocytes in the CNS [159].…”

Section: Clusterinmentioning

confidence: 99%

“…Together with ApoE, clusterin is one of the most abundant apolipoproteins in the brain [159,166]. It participates in multiple biological processes in the body, including removal of cellular debris [167], regulation of programmed cell death [168], lipid transport The mature clusterin is highly N-glycosylated and due to a variable degree of glycosylation, it displays a mass between 58.5-63.5 kDa when analyzed by mass spectrometry.…”

Section: Clusterinmentioning

confidence: 99%

“…Together with ApoE, clusterin is one of the most abundant apolipoproteins in the brain [159,166]. It participates in multiple biological processes in the body, including removal of cellular debris [167], regulation of programmed cell death [168], lipid transport [169], and exhibits a chaperon-like activity in several protein folding processes [169][170][171].…”

Section: Clusterinmentioning

confidence: 99%

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Endogenous Human Proteins Interfering with Amyloid Formation

et al. 2022

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Amyloid formation is a pathological process associated with a wide range of degenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and diabetes mellitus type 2. During disease progression, abnormal accumulation and deposition of proteinaceous material are accompanied by tissue degradation, inflammation, and dysfunction. Agents that can interfere with the process of amyloid formation or target already formed amyloid assemblies are consequently of therapeutic interest. In this context, a few endogenous proteins have been associated with an anti-amyloidogenic activity. Here, we review the properties of transthyretin, apolipoprotein E, clusterin, and BRICHOS protein domain which all effectively interfere with amyloid in vitro, as well as displaying a clinical impact in humans or animal models. Their involvement in the amyloid formation process is discussed, which may aid and inspire new strategies for therapeutic interventions.

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Section: Clusterinmentioning

confidence: 99%

Section: Clusterinmentioning

confidence: 99%

Section: Clusterinmentioning

confidence: 99%

“…Together with ApoE, clusterin is one of the most abundant apolipoproteins in the brain [159,166]. It participates in multiple biological processes in the body, including removal of cellular debris [167], regulation of programmed cell death [168], lipid transport [169], and exhibits a chaperon-like activity in several protein folding processes [169][170][171].…”

Section: Clusterinmentioning

confidence: 99%

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Endogenous Human Proteins Interfering with Amyloid Formation

et al. 2022

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“…A unique aspect of the ER involves glycosylation-assisted folding which is largely mediated by ER resident lectins. There are two calcium-activating chaperones in the ER -calnexin (CNX) and calreticulin (CRT), that associates with glycoproteins and completes the protein folding process [55,59]. The CNX/CRT cycle is critical part of the ER quality control machinery in monitoring the glycosylation and sugar chain structures in protein folding and assembly.…”

Section: Lectin Chaperonesmentioning

confidence: 99%

Cellular Functions of ER Chaperones in Regulating Protein Misfolding and Aggregation: An Emerging Therapeutic Approach for Preeclampsia

Murugesan¹,

Balakrishnan²,

Premkumar³

et al. 2022

Preeclampsia

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Proteinuria is one of the hallmarks of preeclampsia (PE) that differentiates other hypertensive disorders of pregnancy. Protein misfolding and aggregation is an emerging pathological condition underlying many chronic metabolic diseases and neurodegenerative diseases. Recent studies indicate protein aggregation as an emerging biomarker of preeclampsia, wherein several proteins are aggregated and dysregulated in the body fluids of preeclamptic women, provoking the multi-systemic clinical manifestations of the disease. At the cellular level, these misfolded and aggregated proteins are potentially toxic interfering with the normal physiological process, eliciting the unfolded protein response (UPR) pathway activators in the endoplasmic reticulum (ER) that subsequently augments the ER quality control systems to remove these aberrant proteins. ER resident chaperones, folding enzymes and other proteins serve as part of the ER quality control machinery in restoring nascent protein folding. These ER chaperones are crucial for ER function aiding in native protein folding, maintaining calcium homeostasis, as sensors of ER stress and also as immune modulators. Consequently, ER chaperones seems to be involved in many cellular processes, yet the association is expanding to be explored. Understanding the role and mechanism of ER chaperones in regulating protein misfolding and aggregation would provide new avenues for therapeutic intervention as well as for the development of new diagnostic approaches.

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Cholesterol transport and beyond: Illuminating the versatile functions of HDL apolipoproteins through structural insights and functional implications

Bhale,

Meilhac,

d'Hellencourt

et al. 2024

BioFactors

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High‐density lipoproteins (HDLs) play a vital role in lipid metabolism and cardiovascular health, as they are intricately involved in cholesterol transport and inflammation modulation. The proteome of HDL particles is indeed complex and distinct from other components in the bloodstream. Proteomics studies have identified nearly 285 different proteins associated with HDL; however, this review focuses more on the 15 or so traditionally named “apo” lipoproteins. Important lipid metabolizing enzymes closely working with the apolipoproteins are also discussed. Apolipoproteins stand out for their integral role in HDL stability, structure, function, and metabolism. The unique structure and functions of each apolipoprotein influence important processes such as inflammation regulation and lipid metabolism. These interactions also shape the stability and performance of HDL particles. HDLs apolipoproteins have multifaceted roles beyond cardiovascular diseases (CVDs) and are involved in various physiological processes and disease states. Therefore, a detailed exploration of these apolipoproteins can offer valuable insights into potential diagnostic markers and therapeutic targets. This comprehensive review article aims to provide an in‐depth understanding of HDL apolipoproteins, highlighting their distinct structures, functions, and contributions to various physiological processes. Exploiting this knowledge holds great potential for improving HDL function, enhancing cholesterol efflux, and modulating inflammatory processes, ultimately benefiting individuals by limiting the risks associated with CVDs and other inflammation‐based pathologies. Understanding the nature of all 15 apolipoproteins expands our knowledge of HDL metabolism, sheds light on their pathological implications, and paves the way for advancements in the diagnosis, prevention, and treatment of lipid and inflammatory‐related disorders.

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Apolipoprotein J in Alzheimer’s Disease: Shedding Light on Its Role with Cell Signaling Pathway Perspective and Possible Therapeutic Approaches

Cited by 10 publications

References 90 publications

Endogenous Human Proteins Interfering with Amyloid Formation

Endogenous Human Proteins Interfering with Amyloid Formation

Cellular Functions of ER Chaperones in Regulating Protein Misfolding and Aggregation: An Emerging Therapeutic Approach for Preeclampsia

Cholesterol transport and beyond: Illuminating the versatile functions of HDL apolipoproteins through structural insights and functional implications

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