Progressive supranuclear palsy (PSP) is an sporadic, uncommon neurological disorder. It is considered the second most frequent form of atypical parkinsonism. It is characterized by the presence of neurofibrillary tangles in the brainstem, basal ganglia, and cerebellum. Nowadays, there is no apparent trigger of this disease, many MAPT mutations related to the inclusion of exon 10 and environmental factors have been reported as significant risk factors, but much more remains to be elucidated. There exist a wide range of bioinformatics tools, and available microarray databases that could help us study dysregulated cellular and molecular processes leading usto find new therapeutic targets to test possible drugs METHOD: In this study, we seek online available transcriptomic profile data of confirmed PSP patients. We used ArrayExpress microarray dataset from medial temporal lobe (E-MEXP-2280). Raw data were processed and normalized in R system packages; differential expression analysis was performed with limma package, differentially expressed genes (DEGs) were selected with a adjusted p-value<0.05, and a logarithmic fold change greater than 0.5, and minor -0.5, and further functional enrichment analysis and KEGGp analysis were conducted with topGO and limma packages. After differential expression analysis we obtain a total of 640 differentially expressed genes, amount them, 382 were down regulated and 258 upregulated. We observed an increased up-regulated expression of genes related with developmental process, glutamatergic synapse, and transcription activity. And down-regulation of genes related to mRNA processing, endoplasmic reticulum, and extracellular exosome. Our results agree with previous reports, where elevated brain glutamate levels have been found in several brain sites in PSP; also endoplasmic reticulum dysregulated unfolded protein response has been related with PSP pathology. Furthermore, we observe a marked dysregulation of genes involved in mRNA processing, this agrees with previous reports were RNA splicing and RNA binding proteins could be playing an essential physiopathological role in the progression of some tauopathies. We propose that these DEGs could be useful as new biomarkers and possible therapeutic targets for PSP.