Table 1.

Studies supporting the role of retinoids in ALS.

Author	Model	Tissue studied	Main findings
Malaspina [35]	sALS-patients	Spinal cord	Increased RBP1 expression
Corcoran [9]	Wild type rats sALS patients	Spinal cord	Retinol free diet induced a phenotype similar to that observed in ALS rodent models Defects in retinoid receptor subunits and lower levels of expression in retinaldehyde dehydrogenase in humans
Jiang [23]	sALS-patients	Microdissected MNs/spinal cord	Decreased CRABP1 and RARγ expression in microdissected MNs
Jokic [24]	SOD1G93A rats	Spinal cord	Changes in RAR subtypes expression according to disease status. No variations in either retinol binding proteins or metabolic enzymes
Crochemore [49]	SOD1G93A mice	Spinal cord	Treatment with ATRAs (20–30 mg/kg) had a negative effect in mice survival with no particular effect over spinal cord MNs
Kolarcik [27]	sALS/fALS-patients	Spinal cord/MN cultures	Marked alterations in retinoid pathways (binding proteins, receptor subunits) that correlated with MNs survival. Adapalene (RARβ agonist) had a neuroprotective effect in primary-MN cultures
Riancho [42]	SOD1G93A mice	Spinal cord	Bxt (RXR agonist) extended survival, delayed neuromuscular function deterioration and ameliorated MN loss Bxt induced RXR expression, decreased protein aggregation and preserved MN environment

ATRAs (all trans retinoid acid), CRABP1 (cellular retinoid acid binding protein 1), fALS (familiar amyotrophic lateral sclerosis), MN (motor neuron), RAR (retinoic acid receptor), RBP1 (retinol binding protein 1), RXR (retinoid X receptor), and sALS (sporadic amyotrophic lateral sclerosis).