Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder 
characterized by damage of motor neurons. Recent reports indicate that 
inflammatory responses occurring within the central nervous system contribute to 
the pathogenesis of ALS. We aimed to investigate disease-specific gene 
expression associated with neuroinflammation by conducting transcriptome 
analysis on fibroblasts from three patients with sporadic ALS and three normal 
controls. Several pathways were found to be upregulated in patients with ALS, 
among which the toll-like receptor (TLR) and NOD-like receptor (NLR) signaling 
pathways are related to the immune response. Genes-toll-interacting protein 
(TOLLIP), mitogen-activated protein kinase 9 (MAPK9), interleukin-1β (IL-1β), 
interleukin-8 (IL-8), and chemokine (C-X-C motif) ligand 1 (CXCL1)-related to 
these two pathways were validated using western blotting. This study validated 
the genes that are associated with TLR and NLR signaling pathways from different 
types of patient-derived cells. Not only fibroblasts but also induced 
pluripotent stem cells (iPSCs) and neural rosettes from the same origins showed 
similar expression patterns. Furthermore, expression of TOLLIP, a regulator of 
TLR signaling pathway, decreased with cellular aging as judged by changes in its 
expression through multiple passages. TOLLIP expression was downregulated in ALS 
cells under conditions of inflammation induced by lipopolysaccharide. Our data 
suggest that the TLR and NLR signaling pathways are involved in pathological 
innate immunity and neuroinflammation associated with ALS and that TOLLIP, 
MAPK9, IL-1β, IL-8, and CXCL1 play a role in ALS-specific immune responses. 
Moreover, changes of TOLLIP expression might be associated with progression of 
ALS.