Fig. 2: Molecular systems architecture of neuromuscular junction (NMJ) microenvironment signaling in ALS.
From: A molecular systems architecture of neuromuscular junction in amyotrophic lateral sclerosis
In the four-layered architecture, the bottom layer, Triggers, consists of potential triggers: genetic mutations and environmental factors that are implicated in affecting the anatomical components leading to dysfunction in molecular pathways of ALS pathogenesis. The second layer from the bottom, Anatomical Components, consists of the anatomical components of the NMJ: astrocytes, oligodendrocytes, motor neuron terminal, terminal Schwann cell, skeletal muscle endplate, microglia, and endothelial cells that are involved in the pathogenesis of ALS. The third layer from the bottom, Molecular Pathways, consists of the molecular pathways within and among the anatomical components. The top layer, Biological Processes, reveals the three biological processes: neuronal degeneration/death, muscle atrophy, and neuroinflammation, resulting from the dysfunction in molecular pathways of the NMJ microenvironment, leading to ALS. EAAT Excitatory amino acid transporter; NMDA N-methyl D-aspartate, AMPA α-amino-3-hydroxy- 5-methyl-4-isoxazole propionic acid; RhoA Rat sarcoma homolog family member A, ROCK Rho-associated protein kinase, TGF-β Transforming growth factor beta, ER – Endoplasmic reticulum, IL-6 Interleukin-6, Tweak Tumor necrosis factor-like weak inducer of apoptosis, Fn14 Fibroblast growth factor-inducible 14, SOD1 Superoxide dismutase 1, C9ORF72 Chromosome 9 open reading frame 72, TARDBP Trans-activation response DNA binding protein, FUS Fused in sarcoma, UBQLN2 Ubiquilin-2, SQSTM1 Sequestosome 1, TBK1 TANK Binding Kinase 1, VAPB Vesicle-associated membrane protein-associated protein B/C, VCP Valosin-containing protein.
