Clusterin: a multifaceted protein in the brain

Moon, Hee-Jung; Herring, Sarah K; Zhao, Lijun

doi:10.4103/1673-5374.301013

Cited by 16 publications

(7 citation statements)

References 9 publications

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“…Multiple CLU SNPs, both intronic and exonic, have been associated with LOAD (Harold et al, 2009 ; Lambert et al, 2009 ; Moon et al, 2021 ). Interestingly, while some confer protection against AD, others have been linked to an increased AD risk [reviewed in Woody and Zhao ( 2016 )].…”

Section: Clu Isoforms In Admentioning

confidence: 99%

“…A recent publication also describes the effects of removing Exon 2 from CLU and shows downregulation of extracellular matrix pathways in cultured neurons (Foster et al, 2022 ). However, no AD-related CLU mutations have been identified in Exon 2, which harbors the ER-targeting sequence (Moon et al, 2021 ; Foster et al, 2022 ).…”

Section: Clu Function In Admentioning

confidence: 99%

“…The CLU protein is found body wide, including peripheral organs (Ahuja et al, 1996 ; Guo et al, 2016 ; Park et al, 2020 ), the brain (Pasinetti et al, 1994 ; Thambisetty et al, 2013 ; Moon et al, 2021 ), and in bodily fluids (Trougakos and Gonos, 2002 ) such as plasma (De Silva et al, 1990b ; Martinez-Bujidos et al, 2015 ; Hsu et al, 2017 ; Liu et al, 2021 ), urine (Solichova et al, 2007 ), cerebrospinal fluid (Nilselid et al, 2006 ), seminal fluid (Atlas-White et al, 2000 ; Saewu et al, 2017 ), and tears (Yu et al, 2018 ). The functions of CLU in peripheral tissues have been well studied and include the clearance of misfolded proteins (Humphreys et al, 1999 ), lipid transport (Calero et al, 1999 ), inhibition of the complement system (Jenne and Tschopp, 1989 ), and the regulation of oxidative stress and cell death (Foster et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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Clusterin/apolipoprotein J, its isoforms and Alzheimer's disease

Milinkeviciute

Green

2023

Front. Aging Neurosci.

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Section: Clu Isoforms In Admentioning

confidence: 99%

Section: Clu Function In Admentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clusterin/apolipoprotein J, its isoforms and Alzheimer's disease

Milinkeviciute

Green

2023

Front. Aging Neurosci.

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“…It is also known as apolipoprotein J (ApoJ), cytolysis inhibitor (CLI), SP-40, gp80, NA1, NA2, SGP-2, testosterone repressed prostate message 2 (TRPM-2) among many other alternative names [ 37 ]. CLU is expressed in a variety of organs and tissues including the ovary, liver, heart, brain, and adrenal gland [ [37] , [38] , [39] , [40] , [41] , [42] , [43] ]. Although CLU performs homeostatic and physiological functions, it is also involved in pathophysiological processes and is induced by disease and injury [ 44 ].…”

Section: Clusterin (Clu) – Expression and Tissue Distributionmentioning

confidence: 99%

Exploring the translational potential of clusterin as a biomarker of early osteoarthritis

Kalvaityte

Matta

Bernotienė

et al. 2022

Journal of Orthopaedic Translation

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Background Clusterin (CLU; also known as apolipoprotein J) is an ATP-independent holdase chaperone that prevents proteotoxicity as a consequence of protein aggregation. It is a ∼60 kDa disulfide-linked heterodimeric protein involved in the clearance of cellular debris and the regulation of apoptosis. CLU has been proposed to protect cells from cytolysis by complement components and has been implicated in Alzheimer’s disease due to its ability to bind amyloid-β peptides and prevent aggregate formation in the brain. Recent studies suggest that CLU performs moonlighting functions. CLU exists in two major forms: an intracellular form and a secreted extracellular form. The intracellular form of CLU may suppress stress-induced apoptosis by forming complexes with misfolded proteins and facilitates their degradation. The secreted form of CLU functions as an extracellular chaperone that prevents protein aggregation. Methods In this review, we discuss the published literature on the biology of CLU in cartilage, chondrocytes, and other synovial joint tissues. We also review clinical studies that have examined the potential for using this protein as a biomarker in synovial and systemic fluids of patients with rheumatoid arthritis (RA) or osteoarthritis (OA). Results Since CLU functions as an extracellular chaperone, we propose that it may be involved in cytoprotective functions in osteoarticular tissues. The secreted form of CLU can be measured in synovial and systemic fluids and may have translational potential as a biomarker of early repair responses in OA. Conclusion There is significant potential for investigating synovial and systemic CLU as biomarkers of OA. Future translational and clinical orthopaedic studies should carefully consider the diverse roles of this protein and its involvement in other comorbidities. Therefore, future biomarker studies should not correlate circulating CLU levels exclusively to the process of OA pathogenesis and progression. Special attention should be paid to CLU levels in synovial fluid. The Translational potential of this article There is significant potential for investigating synovial and systemic CLU as a predictive biomarker of osteoarthritis (OA) progression and response to novel treatments and interventions. Given that CLU plays diverse roles in other comorbidities such as rheumatoid arthritis (RA) and obesity, future translational and clinical orthopaedic biomarker studies should not directly correlate circulating CLU levels to the process of OA pathogenesis and progression. However, special attention should be paid to CLU levels in synovial fluid. The cytoprotective properties of CLU may support the implementation of regenerative strategies and new approaches for developing targeted therapeutics for OA.

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“…Previous data from the relevant literature has suggested the influence of Sparc protein on collagen (Col6a) fibrils maturation (Rentz et al 2007), and nidogen (I79_015301) is known to interconnect the laminin (Lama) and collagen networks with the assistance of perlecan (Hspg2) to help form a rigid basement membrane (Singh et al 2012). Finally, the biological connection of the members of the last cluster encompassed only three proteins-amyloid-beta A4 protein (App), clusterin (Clu), and an early endosome antigen (Eea1) protein that is known predominantly from Alzheimer's disease research (Wojtas et al 2017(Wojtas et al , 2020Zhao et al 2021). The authors of the latter study found that overexpression of Clu (log2 fold change "feed" vs. "control" day 8 + 0.80) suppresses the formation of amyloid fibrils (log2 fold change "feed" vs. "control" day 8 − 1.88).…”

Section: String Clustering Highlights the Interconnection Of Mitochon...mentioning

confidence: 99%

Hyperosmolality in CHO cell culture: effects on the proteome

Romanova

Schelletter

Hoffrogge

et al. 2022

Appl Microbiol Biotechnol

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Chinese hamster ovary (CHO) cells are the most commonly used host cell lines for therapeutic protein production. Exposure of these cells to highly concentrated feed solution during fed-batch cultivation can lead to a non-physiological increase in osmolality (> 300 mOsm/kg) that affects cell physiology, morphology, and proteome. As addressed in previous studies (and indeed, as recently addressed in our research), hyperosmolalities of up to 545 mOsm/kg force cells to abort proliferation and gradually increase their volume—almost tripling it. At the same time, CHO cells also show a significant hyperosmolality-dependent increase in mitochondrial activity. To gain deeper insight into the molecular mechanisms that are involved in these processes, as detailed in this paper, we performed a comparative quantitative label-free proteome study of hyperosmolality-exposed CHO cells compared with control cells. Our analysis revealed differentially expressed key proteins that mediate mitochondrial activation, oxidative stress amelioration, and cell cycle progression. Our studies also demonstrate a previously unknown effect: the strong regulation of proteins can alter both cell membrane stiffness and permeability. For example, we observed that three types of septins (filamentous proteins that form diffusion barriers in the cell) became strongly up-regulated in response to hyperosmolality in the experimental setup. Overall, these new observations correlate well with recent CHO-based fluxome and transcriptome studies, and reveal additional unknown proteins involved in the response to hyperosmotic pressure by over-concentrated feed in mammalian cells.Key points• First-time comparative proteome analysis of CHO cells exposed to over-concentrated feed.• Discovery of membrane barrier-forming proteins up-regulation under hyperosmolality.• Description of mitochondrial and protein chaperones activation in treated cells.

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Clusterin: a multifaceted protein in the brain

Cited by 16 publications

References 9 publications

Clusterin/apolipoprotein J, its isoforms and Alzheimer's disease

Clusterin/apolipoprotein J, its isoforms and Alzheimer's disease

Exploring the translational potential of clusterin as a biomarker of early osteoarthritis

Hyperosmolality in CHO cell culture: effects on the proteome

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