@misc{10481/58051,
year = {2018},
url = {http://hdl.handle.net/10481/58051},
abstract = {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.},
organization = {J.L.G. was funded by the NIH National Institute of Neurological Disorders and
Stroke (1R03NS087290–01) and Eunice Kennedy Shriver National Institute of
Child Health and Human Development (1R21HD083915-01A1), and the ALS
Therapy Alliance (2013-F-067). The J.L.G.-P. lab is supported by CICE-FEDERP12-
CTS-2256, Plan Nacional de I + D + I 2008–2011 and 2013–2016 (FISFEDER-
PI14/02152), PCIN-2014-115-ERA-NET NEURON II, the European Research
Council (ERC-Consolidator ERC-STG-2012-233764), by an International
Early Career Scientist grant from the Howard Hughes Medical Institute
(IECS-55007420), by The Wellcome Trust-University of Edinburgh Institutional
Strategic Support Fund (ISFF2) and by a private donation by Ms. Francisca
Serrano (Trading y Bolsa para Torpes, Granada, Spain).},
publisher = {Springer Nature},
keywords = {Amyotrophic lateral sclerosis},
keywords = {Human endogenous retrovirus},
keywords = {Retrotransposon},
keywords = {Reverse transcription},
keywords = {Envelope protein},
title = {Transcriptional profiling of HERV-K(HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteins},
doi = {10.1186/s13024-018-0275-3},
author = {Mayer, Jens and Sánchez, Laura and Rodríguez Heras, Sara and García Pérez, José Luis},
}