Overexpression of HGF attenuates the degeneration of Purkinje cells and Bergmann glia in a knockin mouse model of spinocerebellar ataxia type 7

Noma, Satsuki; Ohya-Shimada, Wakana; Kanai, Masanori; Ueda, Keiji; Nakamura, Toshikazu; Funakoshi, Hiroshi

doi:10.1016/j.neures.2012.03.001

Cited by 19 publications

(19 citation statements)

References 27 publications

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“…Transgenic expression of HGF in neurons has exhibited beneficial roles in the animal models of Alzheimer’s disease and polyglutamine diseases [43,130]. Experimental allergic encephalomyelitis that is induced either by immunization with myelin oligodendrocyte glycoprotein peptide or by the adoptive transfer of T cells, which mimics multiple sclerosis, was inhibited in a selective overexpression of HGF by neurons in the central nervous system in mice [57].…”

Section: Hgf As a Biological Drug Candidatementioning

confidence: 99%

HGF–Met Pathway in Regeneration and Drug Discovery

et al. 2014

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Hepatocyte growth factor (HGF) is composed of an α-chain and a β-chain, and these chains contain four kringle domains and a serine protease-like structure, respectively. Activation of the HGF–Met pathway evokes dynamic biological responses that support morphogenesis (e.g., epithelial tubulogenesis), regeneration, and the survival of cells and tissues. Characterizations of conditional Met knockout mice have indicated that the HGF–Met pathway plays important roles in regeneration, protection, and homeostasis in various cells and tissues, which includes hepatocytes, renal tubular cells, and neurons. Preclinical studies designed to address the therapeutic significance of HGF have been performed on injury/disease models, including acute tissue injury, chronic fibrosis, and cardiovascular and neurodegenerative diseases. The promotion of cell growth, survival, migration, and morphogenesis that is associated with extracellular matrix proteolysis are the biological activities that underlie the therapeutic actions of HGF. Recombinant HGF protein and the expression vectors for HGF are biological drug candidates for the treatment of patients with diseases and injuries that are associated with impaired tissue function. The intravenous/systemic administration of recombinant HGF protein has been well tolerated in phase I/II clinical trials. The phase-I and phase-I/II clinical trials of the intrathecal administration of HGF protein for the treatment of patients with amyotrophic lateral sclerosis and spinal cord injury, respectively, are ongoing.

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Section: Hgf As a Biological Drug Candidatementioning

confidence: 99%

HGF–Met Pathway in Regeneration and Drug Discovery

et al. 2014

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“…Similar to pediatric patients, the mice develop a rapidly progressive complex phenotype that includes ataxia, muscle weakness, and severe cone-rod dystrophy, leading to blindness. Interestingly, despite the ubiquitous expression of ataxin-7 266Q, the only abnormal neuronal morphology in the cerebellum is a decrease in the sizes of PCs, whereas the dendritic trees and number of cells appear to be normal (Noma et al, 2012;Yoo et al, 2003). In the end stage of the disease, the mice are hypoactive and die at 19-20 weeks of age (7-8 weeks for homozygous mice) (Yoo et al, 2003).…”

Section: Sca7 Knockin Modelsmentioning

confidence: 99%

“…A more pronounced atrophy and swelling of radial processes is observed in the BG, which also contain the expanded ataxin-7 (Custer et al, 2006) (Figure 64.1). Hepatocyte growth factor (HGF) is a profound regulator of glial metabolism because it is able to upregulate the expression of the key glial proteins GLT-1 (Sun et al, 2002) and GLAST and is known to interfere with cerebellar development (Noma et al, 2012). Interestingly, NIIs first appear in glial cells of nonaffected brain regions and later, after the onset of the overt phenotype, in the cerebellar PCs, hippocampal CA1 pyramidal neurons, and retina.…”

Section: Sca7 Knockin Modelsmentioning

confidence: 99%

“…In the knockin mice, NIIs gradually accumulate in various brain regions and the retinas. Interestingly, overexpression of HGF in SCA7 266Q/5Q animals alleviates PC degeneration, restores glutamate uptake in BG, and improves motor phenotypes (Noma et al, 2012). In the retina, the inclusions appear first in cones and interneurons and later in rods and ganglion cells (Yoo et al, 2003).…”

Section: Sca7 Knockin Modelsmentioning

confidence: 99%

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Mouse Models of SCA3 and Other Polyglutamine Repeat Ataxias

et al. 2015

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“…In the end stage of the disease, the mice are hypoactive and die at 19–20 weeks of age (7–8 weeks as homozygous) [184]. Interestingly, despite the ubiquitous expression of ataxin-7 266Q, the only abnormal neuronal morphology in the cerebellum is a decrease in the sizes of the PCs, whereas the dendritic trees and number of cells appear to be normal [184, 185]. More severe abnormalities are observed in the Bergmann glia, which also express the mutant ataxin-7 [177] (for a map of neuropathology, see Fig.…”

Section: Mouse Models Of Polyq Disordersmentioning

confidence: 99%

Mouse Models of Polyglutamine Diseases: Review and Data Table. Part I

et al. 2012

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Polyglutamine (polyQ) disorders share many similarities, such as a common mutation type in unrelated human causative genes, neurological character, and certain aspects of pathogenesis, including morphological and physiological neuronal alterations. The similarities in pathogenesis have been confirmed by findings that some experimental in vivo therapy approaches are effective in multiple models of polyQ disorders. Additionally, mouse models of polyQ diseases are often highly similar between diseases with respect to behavior and the features of the disease. The common features shared by polyQ mouse models may facilitate the investigation of polyQ disorders and may help researchers explore the mechanisms of these diseases in a broader context. To provide this context and to promote the understanding of polyQ disorders, we have collected and analyzed research data about the characterization and treatment of mouse models of polyQ diseases and organized them into two complementary Excel data tables. The data table that is presented in this review (Part I) covers the behavioral, molecular, cellular, and anatomic characteristics of polyQ mice and contains the most current knowledge about polyQ mouse models. The structure of this data table is designed in such a way that it can be filtered to allow for the immediate retrieval of the data corresponding to a single mouse model or to compare the shared and unique aspects of many polyQ models. The second data table, which is presented in another publication (Part II), covers therapeutic research in mouse models by summarizing all of the therapeutic strategies employed in the treatment of polyQ disorders, phenotypes that are used to examine the effects of the therapy, and therapeutic outcomes.Electronic supplementary materialThe online version of this article (doi:10.1007/s12035-012-8315-4) contains supplementary material, which is available to authorized users.

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Overexpression of HGF attenuates the degeneration of Purkinje cells and Bergmann glia in a knockin mouse model of spinocerebellar ataxia type 7

Cited by 19 publications

References 27 publications

HGF–Met Pathway in Regeneration and Drug Discovery

HGF–Met Pathway in Regeneration and Drug Discovery

Mouse Models of SCA3 and Other Polyglutamine Repeat Ataxias

Mouse Models of Polyglutamine Diseases: Review and Data Table. Part I

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