Vol 2-8 Mini Review

Activation of the ubiquitin-proteasome system: implications for neurodegeneration, aging, and tumorigenesis

Marilene Demasi and Bruna Franciele Faria

Laboratory of Biochemistry and Biophysics, Instituto Butantan, São Paulo-SP, Brazil

Since the discovery of the proteasome (1986), many years passed before researchers explored the benefits of its activation. However, its inhibition, which was first observed in the beginning of the 1990s, gained wide acceptance because of its anti-tumor effect, as proteasome inhibition induces apoptosis. Currently, a proteasome inhibitor is utilized as a clinical tool. However, proteasome activation has been shown to either extend the life span of many cellular and animal models or prevent the accumulation of protein aggregates. Later effect might have an important contribution to neurodegenerative diseases with the hallmark of protein aggregation and the impairment of the proteasome. This short review presents prominent data on proteasome activation, focusing on the 20S catalytic proteasome particle. In addition, the benefits and consequences of proteasome activation in tumor development and progression are discussed.

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Vol 2-8 Commentary

"Commentary: The ageing as a therapeutic target for Alzheimer's disease"

José M. Brito-Armas and Rafael Castro-Fuentes*

Department of Basic Medical Sciences, University of La Laguna, Tenerife, Spain

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Vol 2-8 Commentary

Commentary: Immunohistochemical comparison of astrocytic mGluR5 upregulation in infraorbital nerve- versus sciatic nerve-ligated rat

Benoit Michot1

1Department of Endodontics, New York University - College of Dentistry, 345 E. 24th Street 1008S, New York, NY 10010, United States.

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Vol 2-8 Mini Review

Endothelial prostaglandin E2 regulates neuronal injury after seizure via activation of astrocytes

Takako Takemiya

Medical Research Institute, Tokyo Women’s Medical University, Shinjuku, Tokyo 162-8666, Japan

Astrocytes interact closely with neurons via glutamate; this astrocyte-neuron circuit may play a pivotal role in synaptic transmission. In addition, astrocytes contact vascular endothelial cells (ECs) with their end-feet; therefore, ECs may have some role in regulating neuronal activity via astrocytes in the brain. In our studies, we found that kainic acid (KA) microinjection induced the expression of microsomal prostaglandin E synthase-1 (mPGES-1) in venous ECs and the expression of the prostaglandin E2 (PGE2) receptor EP3 on astrocytes. Moreover, endothelial mPGES-1 exacerbated KA-induced neuronal injury in the mouse brain. In in vitro experiments, mPGES-1 produced PGE2, which increased astrocytic Ca2+ levels and Ca2+-dependent glutamate release, thus aggravating neuronal injury. We found ECs had a role under pathological conditions and brain ECs are not merely a physiological barrier between the blood and brain; instead, they may also act as a signal transducer or amplifier. Moreover, the endothelium-astrocyte-neuron signaling pathway may be crucial for driving neuronal injury elicited by repetitive seizures and may be a new therapeutic target for epilepsy.

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