Abstract
Many studies have revealed a central role of p38 MAPK in neuronal plasticity and the regulation of long-term changes in synaptic efficacy, such as long-term potentiation (LTP) and long-term depression (LTD). However, p38 MAPK is classically known as a responsive element to stress stimuli, including neuroinflammation. Specific to the pathophysiology of Alzheimer’s disease (AD), several studies have shown that the p38 MAPK cascade is activated either in response to the Aβ peptide or in the presence of tauopathies. Here, we describe the role of p38 MAPK in the regulation of synaptic plasticity and its implication in an animal model of neurodegeneration. In particular, recent evidence suggests the p38 MAPK α isoform as a potential neurotherapeutic target, and specific inhibitors have been developed and have proven to be effective in ameliorating synaptic and memory deficits in AD mouse models.
Highlights
The mitogen activated protein kinases (MAPKs) are serine and threonine protein kinases expressed in neuronal and non-neuronal cells in a mature central nervous system (CNS) during a dynamic state in response to various external stimuli, such as growth factors, glutamate and hormones, cellular stress, and pathogens [1]; they mediate proliferation, differentiation, and cell survival [2]
The basic module of MAPK cascades consists of three kinases that act in a sequential manner, namely, MAP kinase kinase kinase (MAPKKK) → MAP kinase kinase (MAPKK) → MAP kinase (MAPK) [3,4]
We provide an overview of the involvement of p38 MAPK in the regulation of synaptic plasticity, its implication in an animal model of neurodegeneration, and its potential as a neurotherapeutic target
Summary
The mitogen activated protein kinases (MAPKs) are serine and threonine protein kinases expressed in neuronal and non-neuronal cells in a mature central nervous system (CNS) during a dynamic state in response to various external stimuli, such as growth factors, glutamate and hormones, cellular stress, and pathogens [1]; they mediate proliferation, differentiation, and cell survival [2]. Reducing p38 MAPK activation by improved synaptic plasticity in angiotensin II-dependent hypertensive mice, either through genetic knock-down or pharmacological inhibition with SKF86002, as assessed by the LTP recording in the hippocampal slices [44].
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