Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Marcie A. Glicksman is active.

Publication


Featured researches published by Marcie A. Glicksman.


Journal of Neurochemistry | 2002

K‐252a Induces Tyrosine Phosphorylation of the Focal Adhesion Kinase and Neurite Outgrowth in Human Neuroblastoma SH‐SY5Y Cells

Anna C. Maroney; Lorraine Lipfert; M. Elizabeth Forbes; Marcie A. Glicksman; Nicola Neff; Robert Siman; Craig A. Dionne

Abstract: The protein kinase inhibitor K‐252a has been shown to promote cholinergic activity in cultures of rat spinal cord and neuronal survival in chick dorsal root ganglion cultures. To determine the mechanism by which K‐252a acts as a neurotrophic factor, we examined the effects of this molecule on a human neuroblastoma cell line, SH‐SY5Y. K‐252a induced neurite outgrowth in a dose‐dependent manner. Coincident with neurite outgrowth was the early tyrosine phosphorylation of 125‐ and 140‐kDa proteins. The phosphorylation events were independent of protein kinase C inhibition because down‐regulation of protein kinase C by long‐term treatment with phorbol ester did not prevent K‐252a‐induced tyrosine phosphorylation. Similarly, the protein kinase C inhibitors H7, GF‐109203X, and calphostin C did not induce the phosphorylation. We have identified one of the phosphosubstrates as the pp125 focal adhesion protein tyrosine kinase (Fak). Induction of phosphorylation coincided with increased Fak activity and appeared to be independent of ligand/integrin interaction. The induction of Fak phosphorylation by K‐252a was also observed in LA‐N‐5 cells and primary cultures of rat embryonic striatal cells but not in PC12 cells. The protein kinase C‐independent induction of tyrosine phosphorylation and the identification of Fak as a substrate of K‐252a‐induced tyrosine kinase activity suggest that this compound mediates neurotrophic effects through a novel signaling pathway.


Journal of Neurochemistry | 1993

K-252a and Staurosporine Promote Choline Acetyltransferase Activity in Rat Spinal Cord Cultures

Marcie A. Glicksman; J. Eric Prantner; Sheryl L. Meyer; M. Elizabeth Forbes; Malini Dasgupta; Michael E. Lewis; Nicola Neff

Abstract: The protein kinase inhibitor K‐252a increased choline acetyltransferase (ChAT) activity in rat embryonic spinal cord cultures in a dose‐dependent manner (EC50 of ∼100 nM) with maximal stimulatory activity at 300 nM resulting in as much as a fourfold increase. A single application of K‐252a completely prevented the marked decline in ChAT activity occurring over a 5‐day period following culture initiation. Of 11 kinase inhibitors, only the structurally related inhibitor Staurosporine also increased ChAT activity (EC50 of ∼0.5 nM). Effective concentrations of K‐252a were not cytotoxic or mitogenic and did not alter the total protein content of treated cultures. Insulin‐like growth factor I, basic fibroblast growth factor, ciliary neurotrophic factor, and leukemia inhibitory factor yielded dose‐dependent increases in ChAT activity in spinal cord cultures. The combination of K‐252a with insulin‐like growth factor‐l or basic fibroblast growth factor increased ChAT activity up to eightfold over that of untreated controls, which was greater than that observed with each compound alone. K‐252a combined with ciliary neurotrophic factor or leukemia inhibitory factor demonstrated no additive or synergistic effects on ChAT activity. These results suggest that there are multiple mechanisms for the regulation of ChAT activity in spinal cord cultures. The enhancement of spinal cord ChAT activity by K‐252a and Staurosporine defines a new neurotrophic activity for these small organic molecules and raises the possibility that they may activate some regulatory elements in common with the ciliary neurotrophic factor and leukemia inhibitory factor family of neurotrophic proteins.


Journal of Neurochemistry | 2002

K‐252a Promotes Survival and Choline Acetyltransferase Activity in Striatal and Basal Forebrain Neuronal Cultures

Marcie A. Glicksman; M. E. Forbes; J. E. Prantner; Nicola Neff

Abstract: The organic molecule K‐252a promoted cell survival, neurite outgrowth, and increased choline acetyltransferase (ChAT) activity in rat embryonic striatal and basal forebrain cultures in a concentration‐dependent manner. A two‐ to threefold increase in survival was observed at 75 nM K‐252a in both systems. A single application of K‐252a at culture initiation prevented substantial (>60%) cell death that otherwise occurred after 4 days in striatal or basal forebrain cultures. A 5‐h exposure of striatal or basal forebrain cells to K‐252a, followed by its removal, resulted in survival equivalent to that observed in cultures continually maintained in its presence. This is in contrast to results found with a 5‐h exposure of basal forebrain cultures to nerve growth factor (NGF). Acute exposure of basal forebrain cultures to K‐252a, but not to NGF, increased ChAT activity, indicating that NGF was required the entire culture period for maximum activity. Striatal cholinergic and GABAergic neurons were among the neurons rescued by K‐252a. Of the protein growth factors tested in striatal cultures (ciliary neurotrophic factor, neurotrophin‐3, NGF, brain‐derived neurotrophic factor, interleukin‐2, basic fibroblast growth factor), only brain‐derived neurotrophic factor promoted survival. The enhancement of survival and ChAT activity of basal forebrain and striatal neurons by K‐252a defines additional populations of neurons in which survival and/or differentiation is regulated by a K‐252a‐responsive mechanism. The above results expand the potential therapeutic targets for these molecules for the treatment of neurodegenerative diseases.


Neuroreport | 1998

CEP-1347/KT7515, a JNK pathway inhibitor, supports the in vitro survival of chick embryonic neurons.

Gian Domenico Borasio; Sonja Horstmann; Johanna Anneser; Nicola Neff; Marcie A. Glicksman

DEVELOPING neurons depend on target-derived trophic factors for survival in vivo and in vitro, which also decrease the activity of c-Jun N-terminal kinase (JNK). We have recently described a survival-promoting effect of inhibitors of cyclin-dependent kinases and JNK on chick peripheral embryonic neurons. Here, we report that the small trophic molecule CEP-1347/KT7515, which has been shown to inhibit the JNK signalling pathway, can promote long term-survival of cultured chick embryonic dorsal root ganglion, sympathetic, ciliary and motor neurons. Because of their pharmacological properties, small trophic molecules such as CEP-1347/KT7515 might be of interest for the treatment of neurodegenerative disorders.


Bioorganic & Medicinal Chemistry Letters | 1995

The effect of Pyrrolo[3,4-c]carbazole derivatives on spinal cord ChAT activity

David P. Rotella; Marcie A. Glicksman; J. Eric Prantner; Nicola Neff; Robert L. Hudkins

Abstract Pyrrolo[3,4-c]carbazole derivatives were prepared as potential neurotrophic agents. The compounds were assayed for their ability to stimulate choline acetyltransferase (ChAT) activity in embryonic rat spinal cord cultures. These simplified K252a derivatives, although less potent and efficacious, have led to the identification of minimal structural requirements for K252a neurotrophic activity.


The Journal of Neuroscience | 1998

Motoneuron Apoptosis Is Blocked by CEP-1347 (KT 7515), a Novel Inhibitor of the JNK Signaling Pathway

Anna C. Maroney; Marcie A. Glicksman; Alie N. Basma; Kevin M. Walton; Ernest Knight; Carol A. Murphy; Becky A. Bartlett; James P. Finn; Thelma S. Angeles; Yuzuru Matsuda; Nicola Neff; Craig A. Dionne


Journal of Neurobiology | 1993

Insulin-like growth factors: putative muscle-derived trophic agents that promote motoneuron survival.

Nicola Neff; David Prevette; Lucien J. Houenou; Michael E. Lewis; Marcie A. Glicksman; Qin-Wei Yin; Ronald W. Oppenheim


Journal of Medicinal Chemistry | 1997

Neurotrophic 3,9-bis[(alkylthio)methyl]-and-bis(alkoxymethyl)-K-252a derivatives.

Masami Kaneko; Yutaka Saito; Hiromitsu Saito; Tadashi Matsumoto; Yuzuru Matsuda; Jeffry L. Vaught; Craig A. Dionne; Thelma S. Angeles; Marcie A. Glicksman; Nicola Neff; David P. Rotella; James C. Kauer; John P. Mallamo; Robert L. Hudkins; Chikara Murakata


Annals of the New York Academy of Sciences | 1993

IGF‐I Supports the Survival and/or Differentiation of Multiple Types of Central Nervous System Neurons

Donna Bozyczko-Coyne; Marcie A. Glicksman; J. Eric Prantner; Beth Ann McKenna; Tom Connors; Connie Friedman; Malini Dasgupta; Nicola Neff


Archive | 1995

Protein kinase inhibitors for treatment of neurological disorders

Michael E. Lewis; James C. Kauer; Nicola Neff; Jill Roberts-Lewis; Chikara Murakata; Hiromitsu Saito; Yuzuru Matsuda; Marcie A. Glicksman; Fumihiko Kanai; Masami Kaneko

Collaboration


Dive into the Marcie A. Glicksman's collaboration.

Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge