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dc.contributor.authorCan Demirdöğen, Birsen
dc.date.accessioned2019-12-25T14:15:47Z
dc.date.available2019-12-25T14:15:47Z
dc.date.issued2019-07
dc.identifier.citationDemirdöğen, B. C. (2019). Potential role of calcifying nanoparticles in the etiology of multiple sclerosis. Medical hypotheses, 128, 25-27.en_US
dc.identifier.issn0306-9877
dc.identifier.urihttps://doi.org/10.1016/j.mehy.2019.05.005
dc.identifier.urihttp://hdl.handle.net/20.500.11851/2888
dc.description.abstractNanobacteria or calcifying nanoparticles are 80–500 nm sized nano-organisms that are physically associated with carbonate apatite mineral formations. They have been indicated in various diseases, including kidney stone formation, Alzheimer's disease, and atherosclerosis. Nanoparticles contain calcium and apatite-binding protein fetuin-A, a calcification inhibitor. However, recent evidence indicates that fetuin-A can form nucleation seeds or nidi that grow in size through ion sedimentation to become larger amorphous nanoparticles in the presence of excess calcium and apatite ions. Fetuin-A also functions as an inhibitor of meprin, a metalloproteinase implicated in inflammation and neurodegenerative diseases. During inflammation, meprin functions to regulate chemokine activity of monocyte chemotactic protein 1, which is associated with chronic inflammatory diseases, including atherosclerosis, renal inflammatory diseases, and multiple sclerosis (MS). In addition, calcium phosphate nanocrystals that contain fetuin-A are pro-inflammatory to macrophages and promote vascular smooth muscle cell mineralization, potentiating a vicious cycle of inflammation and calcification. Thus, mineral stress and inflammation appear to be associated with each other. Furthermore, fetuin-A deficient mice exhibited reduced experimental autoimmune encephalomyelitis severity. Thus, fetuin-A plays a direct role in the neuroinflammatory response. Indeed, the level of fetuin-A in cerebrospinal fluid has been defined as a biomarker of disease activity in MS. MS is a chronic, inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS) with an unknown etiology. The “inside-out” model of MS, supported by recent data, states that the initial axonal degeneration in the CNS occurs before demyelination, which then stimulates an auto-immune attack. It was shown very recently that influx of calcium from the extracellular space through nanoscale ruptures of the axonal plasma membrane predict axon degeneration in neuroinflammation. Calcium is an activator of calpains, proteases that function to break down the cytoskeleton, leading to neurodegeneration. Nanoruptures of the plasma membrane were suggested to occur at the early stages of axon damage, especially at nodes of Ranvier, which are devoid of myelin. Here, I propose that calcifying nanoparticles may have a role in the etiology and/or pathophysiology of MS. The initial event causing neurodegeneration may be due to the nanoparticles that have been suggested to easily cross the blood-brain barrier. Following this, the nanoparticles may create nanoruptures in the axonal membrane and also increase the calcium concentration around and within the neurons by forming nidi for calcification, eventually causing neurodegeneration. Nanoparticles can self-replicate; hence, they may represent an infectious causative agent for the development of MS.en_US
dc.language.isoengen_US
dc.publisherChurchill Livingstoneen_US
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectBiomineralizationen_US
dc.subject Calcifying nanoparticlesen_US
dc.subject Calciprotein particlesen_US
dc.subject Nanobacteriaen_US
dc.subject Nanomedicineen_US
dc.subject Nanonsen_US
dc.subject Nanotoxicologyen_US
dc.titlePotential role of calcifying nanoparticles in the etiology of multiple sclerosisen_US
dc.typearticleen_US
dc.typeinfo:eu-repo/semantics/acceptedVersion
dc.relation.journalMedical Hypothesesen_US
dc.contributor.departmentTOBB ETU, Faculty of Engineering, Department of Biomedical Engineeringen_US
dc.contributor.departmentTOBB ETÜ, Mühendislik Fakültesi, Biyomedikal Mühendisliği Bölümütr_TR
dc.identifier.volume128
dc.identifier.startpage25
dc.identifier.endpage27
dc.contributor.orcidhttps://orcid.org/0000-0002-1536-6123
dc.identifier.wosWOS:000473374600007
dc.identifier.scopus2-s2.0-85065564784
dc.contributor.tobbetuauthorCan Demirdöğen, Birsen
dc.identifier.PubMedIDPMID:31203904
dc.identifier.doi10.1016/j.mehy.2019.05.005
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıtr_TR


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