Table 2.

Proteins found significantly dysregulated in the proteomic analysis and in the literature. All these 14 proteins have consistently been described as dysregulated in previous studies. Therefore our data reinforces the existing knowledge in ALS and the in silico validation shows the robustness of our study.

Gene	Uniprot	Protein Name	p-Value ALS	FC ALS	Molecular Function	Biological Function	ALS-Related
Up-regulated proteins
P4HB	P07237	Protein disulfide-isomerase	0.00	1.07	ER foldase	ER Proteostasis	Mutations and enrichment [28]
VCP	P55072	Transitional endoplasmic reticulum ATPase	0.00	0.71	Multiple functions	DNA Repair/ER Proteostasis	Mutations and enrichment [29]
S100A6	P06703	Protein S100-A6	0.00	1.42	Ca2+/Zn2+ binding protein	calcium sensor and modulator	Enrichment [30]
S100A11	P31949	Protein S100-A11	0.00	2.08	Ca2+/Zn2+ binding protein	calcium sensor and modulator	Enrichment [31]
LGALS3	P17931	Galectin 3	0.01	0.52	Galactose-specific lectin	pre-mRNA splicing factor; acute inflammatory responses	enrichment (tissue, plasma and CSF) [32,33,34]
TTR	P02766	Prealbumin	0.00	1.37	Thyroid hormone-binding protein	thyroxine transport	Down-regulated in blood [35]
Down-regulated proteins
SOD1	P00441	Superoxide dismutase [Cu-Zn]	0.05	−0.32	Multiple functions	Multiple functions	Mutations [36]
INA	Q16352	Alpha-internexin	0.01	−0.95	neuronal intermediate filament	Axonal structure and transport	Down-regulated in motor neurons [37]
NEFM	P07197	Neurofilament medium polypeptide	0.00	−0.71	neuronal intermediate filament	Axonal structure and transport	Down-regulated in CSF [38]
NEFH	P12036	Neurofilament heavy polypeptide	0.00	−0.97	neuronal intermediate filament	Axonal structure and transport	Up-regulated in CSF and Up in plasma [39,40]
TUBA4A	P68366	Tubulin alpha-4A chain	0.00	−1.20	Microtubules structure	Axonal transport	Mutations [41]
CST3	P01034	Cystatin-C	0.01	−0.67	cysteine protease inhibitor	Protein homeostasis	Down-regulated in CSF and up regulated in plasma [42,43]
OPTN	Q96CV9	Optineurin	0.00	−1.03	Multiple functions	Protein homeostasis and vesicle transport	Mutations and enrichment [44]
VAPB	O95292	Vesicle-associated membrane protein-associated	0.01	−0.60	Multiple functions	ER Proteostasis; vesicle transport; calcium homeostasis	Down-regulated in CSF [45]