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 | |
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 | |
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] | |