Transgenic mice overexpressing glia maturation factor-β, an oxidative stress inducible gene, show premature aging due to Zmpste24 down-regulation

Imai, Rika; Asai, Kanae; Hanai, Jun-ichi; Takenaka, Masaru

doi:10.18632/aging.100779

Cited by 6 publications

(2 citation statements)

References 43 publications

(114 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An earlier study has shown that GMF enhances oxidative stress in renal diseases. GMF is normally absent in the kidney but the expression of GMF is inducible in the proximal renal tubules under the stress of proteinuria and in non-brain tissues (Imai et al, 2015 ). Thymus shows the expression of GMF, which is important in T cell development (Utsuyama et al, 2003 ).…”

Section: Gmf In Neuroinflammationmentioning

confidence: 99%

Brain and Peripheral Atypical Inflammatory Mediators Potentiate Neuroinflammation and Neurodegeneration

Kempuraj

Thangavel

Selvakumar

et al. 2017

Front. Cell. Neurosci.

218

180

View full text Add to dashboard Buy / Rent full text

Neuroinflammatory response is primarily a protective mechanism in the brain. However, excessive and chronic inflammatory responses can lead to deleterious effects involving immune cells, brain cells and signaling molecules. Neuroinflammation induces and accelerates pathogenesis of Parkinson’s disease (PD), Alzheimer’s disease (AD) and Multiple sclerosis (MS). Neuroinflammatory pathways are indicated as novel therapeutic targets for these diseases. Mast cells are immune cells of hematopoietic origin that regulate inflammation and upon activation release many proinflammatory mediators in systemic and central nervous system (CNS) inflammatory conditions. In addition, inflammatory mediators released from activated glial cells induce neurodegeneration in the brain. Systemic inflammation-derived proinflammatory cytokines/chemokines and other factors cause a breach in the blood brain-barrier (BBB) thereby allowing for the entry of immune/inflammatory cells including mast cell progenitors, mast cells and proinflammatory cytokines and chemokines into the brain. These peripheral-derived factors and intrinsically generated cytokines/chemokines, α-synuclein, corticotropin-releasing hormone (CRH), substance P (SP), beta amyloid 1–42 (Aβ1–42) peptide and amyloid precursor proteins can activate glial cells, T-cells and mast cells in the brain can induce additional release of inflammatory and neurotoxic molecules contributing to chronic neuroinflammation and neuronal death. The glia maturation factor (GMF), a proinflammatory protein discovered in our laboratory released from glia, activates mast cells to release inflammatory cytokines and chemokines. Chronic increase in the proinflammatory mediators induces neurotoxic Aβ and plaque formation in AD brains and neurodegeneration in PD brains. Glial cells, mast cells and T-cells can reactivate each other in neuroinflammatory conditions in the brain and augment neuroinflammation. Further, inflammatory mediators from the brain can also enter into the peripheral system through defective BBB, recruit immune cells into the brain, and exacerbate neuroinflammation. We suggest that mast cell-associated inflammatory mediators from systemic inflammation and brain could augment neuroinflammation and neurodegeneration in the brain. This review article addresses the role of some atypical inflammatory mediators that are associated with mast cell inflammation and their activation of glial cells to induce neurodegeneration.

show abstract

“…Overexpression of GMFγ in ovarian cancer cells promotes cell migration and invasion, and alters actin organization, and elevated GMFγ levels correlate with poor patient prognosis. Finally, transgenic mice overexpressing GMFβ have shorter lifespans and show accelerated aging particularly in the kidney, suggesting a role for GMF in aging [100].…”

Section: Figurementioning

confidence: 99%

GMF as an Actin Network Remodeling Factor

Goode

Sweeney

Eskin

2018

Trends in Cell Biology

View full text Add to dashboard Buy / Rent full text

Glia maturation factor (GMF) has recently been established as a regulator of the actin cytoskeleton with a unique role in remodeling actin network architecture. Conserved from yeast to mammals, GMF is one of five members of the ADF-H family of actin regulatory proteins, which includes ADF/cofilin, Abp1/Drebrin, Twinfilin, and Coactosin. GMF does not bind actin, but instead binds the Arp2/3 complex with high affinity. Through this association, GMF catalyzes the debranching of actin filament networks and inhibits actin nucleation by Arp2/3 complex. Here, we discuss GMF's emerging role in controlling actin filament spatial organization and dynamics underlying cell motility, endocytosis, and other biological processes. Further, we attempt to reconcile these functions with its earlier characterization as a cell differentiation factor.

show abstract

Transgenic mice overexpressing glia maturation factor-β, an oxidative stress inducible gene, show premature aging due to Zmpste24 down-regulation

Cited by 6 publications

References 43 publications

Brain and Peripheral Atypical Inflammatory Mediators Potentiate Neuroinflammation and Neurodegeneration

GMF as an Actin Network Remodeling Factor

Contact Info

Product

Resources

About