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V. Wee Yong

Bio: V. Wee Yong is an academic researcher from University of Calgary. The author has contributed to research in topics: Multiple sclerosis & Microglia. The author has an hindex of 73, co-authored 233 publications receiving 17556 citations. Previous affiliations of V. Wee Yong include Allen Institute for Brain Science & Foothills Medical Centre.


Papers
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Journal ArticleDOI
TL;DR: Some of the beneficial functions of MMPs during neural development are considered and their roles in repair after brain injury are speculated, as well as a family of proteins known as ADAMs, as some of the properties previously ascribed to M MPs are possibly the result of ADAM activity.
Abstract: Matrix metalloproteinases (MMPs) have been implicated in several diseases of the nervous system. Here we review the evidence that supports this idea and discuss the possible mechanisms of MMP action. We then consider some of the beneficial functions of MMPs during neural development and speculate on their roles in repair after brain injury. We also introduce a family of proteins known as ADAMs (a disintegrin and metalloproteinase), as some of the properties previously ascribed to MMPs are possibly the result of ADAM activity.

1,015 citations

Journal ArticleDOI
TL;DR: General principles that govern the expression of metalloproteinases in the nervous system are discussed and their mechanisms in regulating neurogenesis, myelin formation and axonal growth are focused on.
Abstract: The matrix metalloproteinases and related A disintegrin and metalloproteinase enzymes are implicated in various diseases of the nervous system. However, metalloproteinases are increasingly being recognized as having beneficial roles during nervous system development and following injury. This review discusses general principles that govern the expression of metalloproteinases in the nervous system and their detrimental outcomes. It then focuses on the roles of metalloproteinases and their mechanisms in regulating neurogenesis, myelin formation and axonal growth. It is clear that metalloproteinases are important determinants in enabling recovery from injury to the nervous system.

540 citations

Journal ArticleDOI
TL;DR: The evidence for the efficacy of minocyCline in several animal models of neurological disease is described, the mechanisms by which minocycline affects a range of neurological diseases with diverse causes are discussed, and the emerging investigation of minocrycline in clinical neurology is introduced.
Abstract: Summary The capacity of minocycline to alleviate disease for several neurological disorders in animals is increasingly being recognised. Indeed, that one drug alone can attenuate the severity of disease in stroke, multiple sclerosis, spinal-cord injury, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis is astounding. In this review, we describe the evidence for the efficacy of minocycline in several animal models of neurological disease, discuss the mechanisms by which minocycline affects a range of neurological diseases with diverse causes, and introduce the emerging investigation of minocycline in clinical neurology. The encouraging results of minocycline in experimental neurology bode well for its therapeutic use in human neurological diseases.

481 citations

Journal ArticleDOI
TL;DR: The pathophysiological roles of the brain's ECM, particularly those of CSPGs, after neural insults are highlighted and how the ECM can be targeted to promote remyelination is discussed.
Abstract: The extracellular matrix (ECM) occupies a notable proportion of the CNS and contributes to its normal physiology. Alterations to the ECM occur after neural injury (for example, in multiple sclerosis, spinal cord injury or Alzheimer's disease) and can have drastic consequences. Of note, injury-induced changes in chondroitin sulphate proteoglycans (CSPGs)--a family of ECM proteoglycans--can lead to the inhibition of myelin repair. Here, we highlight the pathophysiological roles of the brain's ECM, particularly those of CSPGs, after neural insults and discuss how the ECM can be targeted to promote remyelination.

421 citations

Journal ArticleDOI
01 Jun 2002-Brain
TL;DR: Results indicate that minocycline may constitute a safe and inexpensive therapy for multiple sclerosis and inhibit MMP activity, reduced production of MMP-9 and decreased the transmigration of T lymphocytes across a fibronectin matrix barrier.
Abstract: Multiple sclerosis is characterized by the infiltration of leukocytes into the CNS. As matrix metalloproteinases (MMPs) facilitate the passage of leukocytes across matrix barriers, we tested the hypothesis that targeting MMPs could attenuate neuro-inflammation. We report that minocycline, a widely used generic drug with a good safety record, inhibited MMP activity, reduced production of MMP-9 and decreased the transmigration of T lymphocytes across a fibronectin matrix barrier. In addition, minocycline was efficacious against both mild and severe experimental autoimmune encephalomyelitis (EAE) in mice, an animal model of multiple sclerosis. When severe EAE was produced, minocycline pre-treatment delayed the course of the disease: when maximal disease activity occurred in vehicle-treated EAE mice, minocycline animals were relatively normal and had minimal signs of inflammation and demyelination in the CNS. When tested in mice afflicted with mild EAE, minocycline attenuated the clinical severity of disease throughout the course of treatment. These results indicate that minocycline may constitute a safe and inexpensive therapy for multiple sclerosis.

418 citations


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Journal ArticleDOI
17 Jul 2014-Immunity
TL;DR: Therapeutic success in targeting these protumoral roles in preclinical models and in early clinical trials suggests that macrophages are attractive targets as part of combination therapy in cancer treatment.

2,945 citations

01 Jan 2013
TL;DR: In this article, the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs) was described, including several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA.
Abstract: We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.

2,616 citations

Journal ArticleDOI
TL;DR: Insight is provided into host–tumour interactions, such as the role of the leukocyte infiltrate, and into the mechanisms that determine the metastatic potential and site-specific spread of cancer cells.
Abstract: A complex network of chemokines and their receptors influences the development of primary tumours and metastases. New information about the biological role of chemokines in these processes is providing insights into host–tumour interactions, such as the role of the leukocyte infiltrate, and into the mechanisms that determine the metastatic potential and site-specific spread of cancer cells. Chemokine-receptor antagonists are showing promise in animal models of inflammation and autoimmune disease. Could manipulating the local chemokine network have therapeutic benefits in malignant disease?

2,214 citations

Journal ArticleDOI
TL;DR: Developments in the signaling mechanisms that regulate specific aspects of reactive astrogliosis are reviewed and the potential to identify novel therapeutic molecular targets for diverse neurological disorders is highlighted.

2,213 citations