2013 Fiscal Year Final Research Report

Therapeutic potential against amyotrophic lateral sclerosis with BAFF which is a novel neurotrophic factor

Research Project

Project/Area Number	24790883
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Neurology
Research Institution	Osaka University
Principal Investigator	TADA Satoru 大阪大学, 医学部附属病院, 医員 (70626530)
Project Period (FY)	2012-04-01 – 2014-03-31
Keywords	神経変性 / 免疫反応 / B細胞 / BAFF / 筋萎縮性側索硬化症(ALS)
Research Abstract	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). 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. 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.