Journal Article

BAFF Controls Neural Cell Survival through BAFF Receptor

Tada, Satoru, Koda, Toru, Nakatsuji, Yuji, Okuno, Tatsusada, Mochizuki, Hideki, Yasui, Teruhito, Sakoda, Saburo, Kikutani, Hitoshi

2013

Overview

Various neuroprotective factors have been shown to help prevention of neuronal cell death, which is responsible for the progression of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). However, most of these therapeutic potentials have been tested by administration of recombinant proteins, transgenic expression or virus vector-mediated gene transfer. Therefore, it remains to be clarified whether any endogenous factors has advantage for neuroprotection in a pathological nervous system. Here we show the role of BAFF-R signaling pathway in the control of neural cell survival. Both B cell-activating factor (BAFF) and its receptor (BAFF-R) are expressed in mouse neurons and BAFF-R deficiency reduces the survival of primary cultured neurons. Although many studies have so far addressed the functional role of BAFF-R on the differentiation of B cells, impaired BAFF-R signaling resulted in accelerated disease progression in an animal model of inherited ALS. We further demonstrate that BAFF-R deficient bone marrow cells or genetic depletion of B cells does not affect the disease progression, indicating that BAFF-mediated signals on neurons, not on B cells, support neural cell survival. These findings suggest opportunities to improve therapeutic outcome for patients with neurodegenerative diseases by synthesized BAFF treatment.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Amyotrophic lateral sclerosis / Animal diseases / Animal models / Animals / B-Cell Activating Factor - genetics / B-Cell Activating Factor - metabolism / B-Cell Activation Factor Receptor - genetics / B-Cell Activation Factor Receptor - metabolism / B-Lymphocytes - metabolism / Biology / BLyS protein / Bone marrow / Bone Marrow Cells - metabolism / Cell death / Cell Line / Cell survival / Cell Survival - genetics / Gene Expression / Gene transfer / Humans / Kinases / Lymphocytes B / Mathematics / Medical treatment / Medicine / Mice / Mice, Knockout / Nervous system / Neurodegeneration / Neurodegenerative diseases / Neurological diseases / Neurons / Neurons - metabolism / Neuroprotection / Proteins / Rodents / Signal transduction / Signaling / Stem cell transplantation / Superoxide Dismutase - genetics / Superoxide Dismutase - metabolism / Superoxide Dismutase-1 / Survival / Viruses