Table 5.
Labeled-MS proteomics studies for mechanistic insight into ALS and FTD.
| Technique | Model | Summary | Remarks | References |
|---|---|---|---|---|
| iTRAQ | SOD1G93A mouse spinal cord | ↑ 676 proteins, ↓ 480 proteins | Preliminary insight into altered proteins | Zhang J. et al., 2018 |
| iTRAQ | Rat neonate spinal cord injected with ALS CSF | ↓ 35 mitochondrial and 4 lysosomal proteins and ↑ BNIP3L | Mitochondrial and lysosomal defects involved in pathogenesis | Sharma et al., 2016 |
| SILAC | HeLa cells expressing FUS/TLS | ↑ FUS/TLS mutant interaction with SMN and ↓ interaction with U1-snRNP | Demonstrates a gain and loss of function in FUS-ALS | Sun et al., 2015 |
| SILAC | Primary mouse astrocyte cultures | 60 astrocyte proteins regulate secretion with Ang stimulation | Ang taken up by astrocytes = potential neuroprotection | Skorupa et al., 2013 |
| SILAC | HEK-293 cells expressing TDP-43 or splice variant | 35 proteins co-aggregate with TDP-43 (G3BP, PABPC1 and eIF4A1), 4 ubiquitinated sites on TDP-43 splice variant | TDP-43 aggregation partners + ubiquitination affects oligomerization | Dammer et al., 2012 |
| SILAC and label-free | H1299 cells and HEK293T cells expressing UBXD1 or ERGIC-53 | Interactome of UBXD1 includes VCP and ERGIC-53, highlighting its role in vesicle trafficking | UBXD1 involved in regulation of ERGIC-53 trafficking through its interaction with VCP | Haines et al., 2012 |
| SILAC and label-free | HeLa cells expressing TDP-43 | TDP-43 interacts with hnRNP, Drosha and FUS/TLS complexes, mutant TDP-43 ↑ FUS/TLS interactions | TDP-43 involved in mRNA processing and miRNA biogenesis, function overlap with FUS | Ling et al., 2010 |
| TMT | C9ALS and sALS iPSCs | RNA stability/binding targets: ↑/↓ 170 altered in C9ALS and 121 in sALS | Destabilization of RNA transcripts involved in oxidative phosphorylation and ribosomal machinery | Tank et al., 2018 |
| TMT | hESC and hESC MN cells expressing C9ORF72, immunoprecipitated | C9ORF72 stabilizes SMCR8, enables interaction with WDR41 | C9ORF72+SMCR8 involved in autoimmunity and lysosomal exocytosis | Zhang Y. et al., 2018 |
| TMT | HeLa cells expressing C9ORF72 DPR proteins | C9ORF72 PR and GR DPRs block spliceosome assembly | DPR-mediated dysfunction = Mis-spliced exons in C9ORF72 | Yin et al., 2017 |
| TMT | C57BL/6J tau KO mouse brain | Interactome of tau and isoforms – 101 proteins identified | Selective binding of proteins with specific isoforms of tau | Liu et al., 2016 |
| TMT and iTRAQ | HEK293T and SH-SY5Y expressing various tau proteins | TauP301L disrupts interactions with heat shock, proteasome and microtubule-associated proteins | Mutant tauP301L ↓ interactions with chaperones and proteasome | Gunawardana et al., 2015 |
↑, denotes increase; ↓, denotes decrease; Ang, angiogenin; BNIP3L, BCL2 interacting protein 3-like; CSF, cerebrospinal fluid; DPR, dipeptide repeat; eIF4A1, eukaryotic translation initiation factor 4A1; ERGIC-53, ER-Golgi intermediate compartment 53 kDa protein; FTD, frontotemporal dementia; FUS, fused-in-sarcoma; G3BP, ras GTPase-activating protein; GR, glycine arginine; hESC, human embryonic stem cell; iTRAQ, isobaric tags for relative and absolute quantitation; KO, knockout; MN, motor neuron; PABPC1, polyadenylate-binding protein 1; PR, proline arginine; sALS, sporadic amyotrophic lateral sclerosis; SILAC, stable isotope labeling by amino acids in cell culture; SMCR8, guanine nucleotide exchange protein; SMN, survival motor neuron protein; TDP-43, TAR DNA binding protein of 43 kDa; TMT, tandem mass tag; UBXD1, UBX domain-containing protein 1; VCP, valoslin-containing protein; and WDR41, WD repeat-containing protein 41.