Nociceptive and behavioural sensitisation by protein kinase Cɛ signalling in the CNS

Abstract

Despite the apparent homology in the protein kinase C (PKC) family, it has become clear that slight structural differences are sufficient to have unique signalling properties for each individual isoform. For PKCɛ in depth investigation of these aspects revealed unique actions in the CNS and lead to development of specific modulators with clinical perspective. In this review, we describe to which extent PKCɛ is distinct from other isoforms on the level of tissue expression and protein structure. As this kinase is highly expressed in the brain, we outline three main aspects of PKCɛ signalling in the CNS. First, its ability to alter the permeability of N‐type Ca2+ channels in dorsal root ganglia has been shown to enhance nociception. Secondly, PKCɛ increases anxiety by diminishing GABAAR‐induced inhibitory post‐synaptic currents in the prefrontal cortex. Another important aspect of the latter inhibition is the reduced sensitivity of GABAA receptors to ethanol, a mechanism potentially contributing to abuse. A third signalling cascade improves cognitive functions by facilitating cholinergic signalling in the hippocampus. Collectively, these findings point to a physical and behavioural sensitising role for this kinase.

Reduction of β-Amyloid Levels by Novel Protein Kinase Cϵ Activators

“…PKC⑀ is expressed at very low levels in all normal tissues except for brain (29,30). Wetsel et al (31) reported that PKC⑀ and PKC⑀ Ј are expressed predominantly in brain, with very weak staining in other tissues.…”

The hippocampus and TNF: Common links between chronic pain and depression

“…Physiological and psychological stresses trigger a variety of signals that affect behavior and the systemic and metabolic processes that are responsible for coping with these changes. Alteration of these signaling systems, as those seen in persistent chronic painful stimuli, may lead to the development of depressive disorders (Henn and Vollmayr, 2005;Van Kolen et al, 2008).…”

The role of protein kinase C epsilon in neural signal transduction and neurogenic diseases

“…Protein kinase C epsilon (PKC ε), one of the PKC family members, is a protein catalyzing a variety of Ser/Thr residues phosphorylated, which has been shown to be involved in many different cellular functions, such as cellular processes, proliferation, differentiation, neuronal plasticity, endocrine, exocrine, cardiovascular mechanism, inflammatory processes, gene expression, regulation of cell growth, ion channels activity and receptors desensitization [1][2][3][4][5][6]. In this review, we focus on the recent progress of the role of PKC ε in development of neurons and associated neural diseases.…”