Expression of HERV Genes as Possible Biomarker and Target in Neurodegenerative Diseases

Human endogenous retroviruses (HERVs) are genetic parasites, in-between genetics and
environment. Few HERVs retain some coding capability. Sometimes, the host has the advantage of
some HERV genes; conversely, HERVs may contribute to pathogenesis. The expression of HERVs
depends on several factors, and is regulated epigenetically by stimuli such as inflammation, viral and
microbial infections, etc. Increased expression of HERVs occurs in physiological and pathological
conditions, in one or more body sites. Several diseases have been attributed to one or more HERVs,
particularly neurological diseases. The key problem is to dierentiate the expression of a HERV as
cause or eect of a disease. To be used as a biomarker, a correlation between the expression of a certain
HERV and the disease onset and/or behavior must be found. The greater challenge is to establish
a pathogenic role. The criteria defining causal connections between HERVs and diseases include
the development of animal models, and disease modulation in humans, by anti-HERV therapeutic
antibody. So far, statistically significant correlations between HERVs and diseases have been achieved
for HERV-W and multiple sclerosis; disease reproduction in transgenic animals was achieved for
HERV-W and multiple sclerosis, and for HERV-K and amyotrophic lateral sclerosis. Clinical trials for
both diseases are in progress.