Heparanase: Potential roles in multiple sclerosis

Changyaleket, Benjarat; Deliu, Zanë; Chignalia, Andréia Z.; Feinstein, Douglas L.

doi:10.1016/j.jneuroim.2017.07.001

Cited by 15 publications

(13 citation statements)

References 128 publications

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“…HSPGs are found throughout neural ECM and have been found localized with Aβ amyloid plaques and neurofibrillary tangles in AD patients [107], having potentially been secreted by activated glial cells [109]. HSPGs have also been associated with ALS pathology [110], PD pathology [111], and MS pathology [112]. Furthermore, HSPGs are involved in blood brain barrier (BBB) organization [113] and control the ability of monocytes to cross the BBB [114].…”

Section: Discussionmentioning

confidence: 99%

Panoramic Visualization of Circulating MicroRNAs Across Neurodegenerative Diseases in Humans

Brennan¹,

Keon²,

Liu³

et al. 2019

Mol Neurobiol

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Neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and dementia pose one of the greatest health challenges this century. Although these NDs have been looked at as single entities, the underlying molecular mechanisms have never been collectively visualized to date. With the advent of high-throughput genomic and proteomic technologies, we now have the opportunity to visualize these diseases in a whole new perspective, which will provide a clear understanding of the primary and secondary events vital in achieving the final resolution of these diseases guiding us to new treatment strategies to possibly treat these diseases together. We created a knowledge base of all microRNAs known to be differentially expressed in various body fluids of ND patients. We then used several bioinformatic methods to understand the functional intersections and differences between AD, PD, ALS, and MS. These results provide a unique panoramic view of possible functional intersections between AD, PD, MS, and ALS at the level of microRNA and their cognate genes and pathways, along with the entities that unify and separate them. While the microRNA signatures were apparent for each ND, the unique observation in our study was that hsa-miR-30b-5p overlapped between all four NDS, and has significant functional roles described across NDs. Furthermore, our results also show the evidence of functional convergence of miRNAs which was associated with the regulation of their cognate genes represented in pathways that included fatty acid synthesis and metabolism, ECM receptor interactions, prion diseases, and several signaling pathways critical to neuron differentiation and survival, underpinning their relevance in NDs. Envisioning this group of NDs together has allowed us to propose new ways of utilizing circulating miRNAs as biomarkers and in visualizing diverse NDs more holistically . The critical molecular insights gained through the discovery of ND-associated miRNAs, overlapping miRNAs, and the functional convergence of microRNAs on vital pathways strongly implicated in neurodegenerative processes can prove immensely valuable in the identifying new generation of biomarkers, along with the development of miRNAs into therapeutics.Electronic supplementary materialThe online version of this article (10.1007/s12035-019-1615-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Panoramic Visualization of Circulating MicroRNAs Across Neurodegenerative Diseases in Humans

Brennan¹,

Keon²,

Liu³

et al. 2019

Mol Neurobiol

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“…It is thought that the pattern, epimerization, and degree of sulfation is important in facilitating HS-ligand interactions, thereby enabling HS to function as a key regulator of complex cell signaling mechanisms in development, regulation of chemokine function, angiogenesis, and blood coagulation, in both normal and disease states (Bishop, Schuksz, & Esko, 2007;Changyaleket, Deliu, Chignalia, & Feinstein, 2017;Cui, Freeman, Jacobson, & Small, 2013). They exist as proteoglycans (HSPG) in which two or three HS chains are attached to core proteins at the cell surface, or extracellular matrix (ECM) proteins.…”

mentioning

confidence: 99%

“…They exist as proteoglycans (HSPG) in which two or three HS chains are attached to core proteins at the cell surface, or extracellular matrix (ECM) proteins. It is thought that the pattern, epimerization, and degree of sulfation is important in facilitating HS-ligand interactions, thereby enabling HS to function as a key regulator of complex cell signaling mechanisms in development, regulation of chemokine function, angiogenesis, and blood coagulation, in both normal and disease states (Bishop, Schuksz, & Esko, 2007;Changyaleket, Deliu, Chignalia, & Feinstein, 2017;Cui, Freeman, Jacobson, & Small, 2013). To investigate how HS sulfation characteristics influence astrocytosis, we applied a panel of modified heparins (mHeps) which have been selectively desulfated to the confrontation assay.…”

mentioning

confidence: 99%

Low sulfated heparins target multiple proteins for central nervous system repair

McCanney

McGrath

Otto

et al. 2018

Glia

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The lack of endogenous repair following spinal cord injury (SCI) accounts for the frequent permanent deficits for which effective treatments are absent. Previously, we demonstrated that low sulfated modified heparin mimetics (LS‐mHeps) attenuate astrocytosis, suggesting they may represent a novel therapeutic approach. mHeps are glycomolecules with structural similarities to resident heparan sulfates (HS), which modulate cell signaling by both sequestering ligands, and acting as cofactors in the formation of ligand–receptor complexes. To explore whether mHeps can affect the myelination and neurite outgrowth necessary for repair after SCI, we created lesioned or demyelinated neural cell co‐cultures and exposed them with a panel of mHeps with varying degrees and positions of their sulfate moieties. LS‐mHep7 enhanced neurite outgrowth and myelination, whereas highly sulfated mHeps (HS‐mHeps) had attenuating effects. LS‐mHeps had no effects on myelination or neurite extension in developing, uninjured myelinating cultures, suggesting they might exert their proregenerating effects by modulating or sequestering inhibitory factors secreted after injury. To investigate this, we examined conditioned media from cultures using chemokine arrays and conducted an unbiased proteomics approach by applying TMT‐LC/MS to mHep7 affinity purified conditioned media from these cultures. Multiple protein factors reported to play a role in damage or repair mechanisms were identified, including amyloid betaA4. Amyloid beta peptide (1–42) was validated as an important candidate by treating myelination cultures and shown to inhibit myelination. Thus, we propose that LS‐mHeps exert multiple beneficial effects on mechanisms supporting enhanced repair, and represent novel candidates as therapeutics for CNS damage.

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“…Heparan sulfate proteoglycans (HSPGs) are mainly present in the ECM and in the cell cytoplasmatic membrane and bind the Heparan sulfate (HS) chains (Lu et al, 2011). Syndecans (SDC) are HSPGs acting as regulators of cell migration, endocytosis, and cell signals (Beauvais and Rapraeger, 2003;Afratis et al, 2012;Christianson and Belting, 2014;Gallagher, 2015;Changyaleket et al, 2017). HS chains, according to their different degree of sulfation, can interfere with the growth factors/ receptors interplay and promote the signal activation (Lu et al, 2011;Changyaleket et al, 2017).…”

Section: Midkine Heparan Sulfate and Extracellular Matrix: A Role Fmentioning

confidence: 99%

Physiology of Midkine and Its Potential Pathophysiological Role in COVID-19

2020

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SARS-CoV2 infection not only causes abnormal severe pneumonia but also induces other relevant pathophysiological effects on several tissues and organs. In this regard, the clinical complications observed in COVID-19 include acute coronary syndrome, pulmonary thromboembolism, myocarditis and, in the severe cases, the occurrence of disseminated intravascular coagulation. Literature on COVID-19 highlighted the central role of the Renin Angiotensin Aldosterone System in the determinism of SARS-CoV2 cellular internalization in the target tissues. Lung degeneration and respiratory distress appear to be dependent on the perturbance of physiological mechanisms, such as the uncontrolled release of pro-inflammatory cytokines, a dysregulation of the fibrinolytic coagulative cascade and the hyperactivation of immune effector cells. In this mini review, we address the physiology of Midkine, a growth factor able to bind heparin, and its pathophysiological potential role in COVID-19 determinism. Midkine increases in many inflammatory and autoimmune conditions and correlates with several dysfunctional immune-inflammatory responses that appear to show similarities with the pathophysiological elicited by SARS-CoV2. Midkine, together with its receptor, could facilitate the virus entry, fostering its accumulation and increasing its affinity with Ace2 receptor. We also focus on Netosis, a particular mechanism of pathogen clearance exerted by neutrophils, which under certain pathological condition becomes dysfunctional and can cause tissue damage. Moreover, we highlight the mechanism of autophagy that the new coronavirus could try to escape in order to replicate itself, as well as on pulmonary fibrosis induced by hypoxia and on the release of cytokines and mediators of inflammation, correlating the interplay between Midkine and SARS-CoV2.

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Heparanase: Potential roles in multiple sclerosis

Cited by 15 publications

References 128 publications

Panoramic Visualization of Circulating MicroRNAs Across Neurodegenerative Diseases in Humans

Panoramic Visualization of Circulating MicroRNAs Across Neurodegenerative Diseases in Humans

Low sulfated heparins target multiple proteins for central nervous system repair

Physiology of Midkine and Its Potential Pathophysiological Role in COVID-19

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