Neurodegenerative diseases affect millions of people worldwide. The symptoms of neurodegeneration are caused by the progressive loss of neurons in the central or peripheral nervous system. Protein aggregation into insoluble inclusion bodies is one of the main hallmarks of neurodegeneration. TAR (Trans Activation Response) DNA-binding protein 43 (TDP-43) is one of the critical proteins in neurodegeneration. In normal cells, TDP-43 is mainly present in the nucleus and plays an important role in RNA regulation. Under pathological conditions, cleavage, hyperphosphorylation and ubiquitination of TDP-43 can occur. These posttranslational modifications lead to cytoplasmic accumulation and aggregation of TDP-43. Another critical protein in neurodegeneration is the chaperone at the endoplasmic reticulum (ER) Sigma receptor 1 (Sig-1R). Dysregulation of TDP-43 can be directly caused by Sig-1R aggregation. ER chaperone Sig-1R accumulates in motor neurons of ALS patients and may have neuroprotective functions. In our work we focused on the in vitro aggregation of TDP-43 and the influence of the Sig-1R protein on the course of TDP-43 aggregation. We expressed TDP-43_MBP and Sig-1R protein lacking N-terminal transmembrane region (ΔNSig-1R) in E.coli BL21[DE3] cells. In the process of protein purification with affinity chromatography and size-exclusion chromatography we isolated enough soluble TDP-43-MBP and ΔNSig-1R for further aggregation and interaction experiments. To analyze TDP-43 aggregation, we utilized spectrofotometric turbidity measurements (optical density at 395 nm). Aggregation was followed in the presence of a previously known aggregation inhibitor tRNA and a hypothetical inhibitor ΔNSig-1R. Addition of tRNA decreased or prevented aggregation of TDP-43. Addition of ΔNSig-1R did not prevent TDP-43 aggregation. We utilized bio-layer interferometry (BLI) for interaction analysis of TDP-43 with tRNA and ΔNSig-1R. There was a weak interaction between TDP-43 and tRNA as well as ΔNSig-1R, but due to technical errors during our work, the experiment should be repeated.