The role of intracellular signaling molecules in the production of granulocytic CSF mononuclear phagocytes in stress and cytostatic influence

Abstract Objectives The development of approaches to the treatment of neurodegenerative diseases caused by alcohol abuse by targeted pharmacological regulation of intracellular signaling transduction of progenitor cells of nerve tissue is promising. We studied peculiarities of participation of NF-кB-, сАМР/РКА-, JAKs/STAT3-, ERK1/2-, p38-pathways in the regulation of neural stem cells (NSC) and neuronal-committed progenitors (NCP) in the simulation of ethanol-induced neurodegeneration in vitro and in vivo. Methods In vitro, the role of signaling molecules (NF-кB, сАМР, РКА, JAKs, STAT3, ERK1/2, p38) in realizing the growth potential of neural stem cells (NSC) and neuronal-committed progenitors (NCP) in ethanol-induced neurodegeneration modeled in vitro and in vivo was studied. To do this, the method of the pharmacological blockade with the use of selective inhibitors of individual signaling molecules was used. Results Several of fundamental differences in the role of certain intracellular signaling molecules (SM) in proliferation and specialization of NSC and NCP have been revealed. It has been shown that the effect of ethanol on progenitors is accompanied by the formation of a qualitatively new pattern of signaling pathways. Data have been obtained on the possibility of stimulation of nerve tissue regeneration in ethanol-induced neurodegeneration by NF-кB and STAT3 inhibitors. It has been found that the blockage of these SM stimulates NSC and NCP in conditions of ethanol intoxication and does not have a «negative» effect on the realization of the growth potential of intact progenitors (which will appear de novo during therapy). Conclusions The results may serve as a basis for the development of fundamentally new drugs to the treatment of alcoholic encephalopathy and other diseases of the central nervous system associated with alcohol abuse.

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I. Cellular and molecular biology of sodium channel β-subunits: therapeutic implications for pain?

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2000.278.3.g349 ◽

2000 ◽

Vol 278 (3) ◽

pp. G349-G353 ◽

Cited By ~ 18

Author(s):

Lori L. Isom

Keyword(s):

Sodium Channel ◽

Intracellular Signaling ◽

Signaling Molecules ◽

Pain Mechanisms ◽

Therapeutic Implications ◽

Channel Modulation ◽

Intimate Association ◽

Intracellular Signaling Molecules ◽

Α Subunits

Voltage-gated sodium channel α-subunits have been shown to be key mediators of the pathophysiology of pain. The present review considers the role of sodium channel auxiliary β-subunits in channel modulation, channel protein expression levels, and interactions with extracellular matrix and cytoskeletal signaling molecules. Although β-subunits have not yet been directly implicated in pain mechanisms, their intimate association with and ability to regulate α-subunits predicts that they may be a viable target for therapeutic intervention in the future. It is proposed that multifunctional sodium channel β-subunits provide a critical link between extracellular and intracellular signaling molecules and thus have the ability to fine tune channel activity and electrical excitability.

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