Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons. There are several mutations that can lead to the development of this disease, including the SOD-1 gene. Riluzole is the only approved drug to slow the progression of the disease and to promote longer survival. However, its effects are limited. Therefore, it is necessary to develop new therapies for ALS treatment. Previous studies have suggested trehalose and vitamin E, individually, as good candidates for ALS treatment. In order to associate these molecules, we developed nanocapsules and nanoemulsions of trehalose and vitamin E and exposed to Caenorhabditis elegans (C. elegans) ALS model and evaluated the pharmacological potential of these nanoparticles. Pregnant AM263 [
unc-54p::
Hsa-sod-1 (WT)::YFP] and AM265 [Punc-54::hSOD1(G93A)::YFP] worms were synchronized. The eggs obtained from these nematodes were transferred to Petri dishes previously dried containing NGM medium and UV-inactivated E.coli OP50 with or without treatment. Trehalose/vitamin E nanomaterials were provided by a partner laboratory. The treatment was performed with nanoparticles pipetted on NGM surface. When the worms reached L4 stage, they were transferred to new plates containing or not nanoparticles. This process was performed from day 1 adult until 4th day adult. Nematode paralysis was assessed along longevity; nematodes were considered paralyzed if they did not move when prodded with a wire pick. SOD-::GFP aggregation was observed at 5th day adult through fluorescence microscope. Our data showed that the nanoparticles decreased the number of paralyzed worms and increased their longevity. Besides that, the treatment with Vit. E+ trehalose nanoparticles provided a slight modification in the SOD1 aggregation profile. ALS promote motor neuron disabling, leading to muscular paralysis and death. This way, these results suggest a great advantage of nanoparticles in mitigating the main effects caused by ALS. There are studies reporting the protective effect of sugars, such as sucrose, however, these carbohydrates have many disadvantages. Trehalose is more cost-effective than other sugars, in addition to having neuroprotective and autophagosome modulating activity. In turn, vitamin E is an antioxidant widely used in several pharmacological area including in neuronal studies. In conclusion, the association of these two compounds proved to be efficient in the ALS treatment.