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Table 2 Role of ALS/FTLD associated proteins in cellular or whole body metabolism

From: Disease-modifying effects of metabolic perturbations in ALS/FTLD

Protein Model Molecular manipulation Implication of the protein in metabolic pathways Citation
TDP-43 Mice Tardbp conditional neuromuscular knock-out Regulation of obesity-associated gene Tbc1d1 Chiang et al. [24]
Mice Tardbp neuromuscular over-expression Regulation of glucose transporter GLUT4 translocation Stallings et al. [161]
Mice Knock-in of human hTDP-43A315T Regulation of fatty acid transporter CD36 Stribl et al. [164]
HCC cell line TARDBP RNAi Regulation of rate-limiting enzyme of glycolysis PFKP Park et al. [131]
iPSC-derived neurons from ALS/FTLD Over-expression of disease-linked TARDBP mutations Disruption of mitochondrial complex I assembly by TDP-43 pathological mis-localization in ALS/FTLD Wang et al. [181]
PGRN Mice IP injections of recombinant PGRN protein Control of insulin-resistance, obesity, and adipose tissue dynamics through IL-6 and TNF-α Zhou et al. [196]
Mice IP injections of recombinant PGRN protein Regulation of insulin sensitivity through PERK-eIF2α axis Li et al. [90]
TREM2 Mice Trem2 over-expression Regulation of adipogenesis and adipocyte differentiation through Wnt-1/β-Catenin signaling Park et al. [128, 129]
Mice Trem2 over-expression Regulation of insulin resistance and hepatic steatosis Park et al. [130]
FUS Drosophila Mutant human FUS over-expression Fragmentation of mitochondria caused by pathological aggregation of FUS to mitochondria Deng et al. [39]
N2a cell line Mutant human FUS over-expression Mutant FUS interacts with enzymes involved in glucose metabolism
Regulation of ATP production
Wang et al. [180]
NSC34 cell line Mutant human FUS over-expression Regulation of ATP production Stoica et al. [163]
EWS Mice EWS knock-out Regulation of mitochondrial density in pre-adipocytes Park et al. [128, 129]
C9ORF72 Motor neurons and lymphoblastoid cell lines from ALS patients with C9ORF72 expansion Regulation of genes involved in cholesterol biosynthesis and glucose metabolism Cooper-Knock et al. [27]
  1. Abbreviations: TDP-43/ Tardbp Tat activating responsive DNA binding protein, PGRN Progranulin, TREM2/Trem2 Triggering receptor expressed on myeloid cells 2, FUS/FUS Fused in sarcoma, EWS/EWS Ewing’s sarcoma, C9ORF72 Chromosome 9 open reading frame 72, HCC Hepatocellular carcinoma, iPSC induced pluripotent stem cells, N2a Neuroblastoma, NSC34 Motor- neuron like cells, RNAi RNA interference, Tbc1d1 Tre-2/Bub2/Cdc16 1 domain family member 1, GLUT4 Glucose transporter 4, CD36 cluster of differentiation 36, PFKP Phosphofructokinase, IL-6 Interleukin 6, TNF-α Tumor necrosis factor alpha, PERK Protein kinase RNA-like endoplasmic reticulum kinase, eIF2α Eukaryotic initiation factor alpha