Transcriptional profiling of HERV-K(HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteins Mayer, Jens Sánchez, Laura Rodríguez Heras, Sara García Pérez, José Luis Amyotrophic lateral sclerosis Human endogenous retrovirus Retrotransposon Reverse transcription Envelope protein Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. About 90% of ALS cases are without a known genetic cause. The human endogenous retrovirus multi-copy HERV-K(HML-2) group was recently reported to potentially contribute to neurodegeneration and disease pathogenesis in ALS because of transcriptional upregulation and toxic effects of HML-2 Envelope (Env) protein. Env and other proteins are encoded by some transcriptionally active HML-2 loci. However, more detailed information is required regarding which HML-2 loci are transcribed in ALS, which of their proteins are expressed, and differences between the disease and non-disease states. We identified 24 different transcribed HML-2 loci. Some of those loci are transcribed at relatively high levels. However, significant differences in HML-2 loci transcriptional activities were not seen when comparing ALS and controls. Likewise, overall HML-2 transcript levels, as determined by RT-qPCR, were not significantly different between ALS and controls. Indeed, we were unable to detect full-length HML-2 Env protein in ALS and control tissue samples despite reasonable sensitivity. Rather our analyses suggest that a number of HML-2 protein variants other than full-length Env may potentially be expressed in ALS patients. Our results expand and refine recent publications on HERV-K(HML-2) and ALS. Some of our results are in conflict with recent findings and call for further specific analyses. Our profiling of HML-2 transcription in ALS opens up the possibility that HML-2 proteins other than canonical full-length Env may have to be considered when studying the role of HML-2 in ALS disease. 2019-11-25T12:29:49Z 2019-11-25T12:29:49Z 2018 info:eu-repo/semantics/article Mayer, J., Harz, C., Sanchez, L., Pereira, G. C., Maldener, E., Heras, S. R., ... & García-Pérez, J. L. (2018). Transcriptional profiling of HERV-K (HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteins. Molecular neurodegeneration, 13(1), 39. http://hdl.handle.net/10481/58051 10.1186/s13024-018-0275-3 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España Springer Nature