Human Endogenous Retroviruses as Novel Therapeutic Targets in Neurodegenerative Disorders
Elena Rita Simula, Seyedesomaye Jasemi, Davide Cossu, Milena Fais, Irene Cossu, Vanna Chessa, Mattia Canu, Leonardo A. Sechi
Abstract
Human Endogenous Retroviruses comprise approximately 8% of the human genome, serving as fragments of ancient retroviral infections. Although they are generally maintained in a silenced state by robust epigenetic mechanisms, specific HERV groups, particularly HERV-W and HERV-K, can become derepressed under specific pathological conditions, thereby contributing to the initiation and progression of neuroinflammatory and neurodegenerative processes. Preclinical studies and clinical trials, such as those investigating monoclonal antibodies, indicate that directly targeting these elements may offer a novel therapeutic strategy. In this review, we provide an overview of HERVs' biology, examine their role in neurodegenerative diseases such as amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer's disease, and Parkinson's disease, and explore their therapeutic prospects, highlighting both the challenges and the potential future research directions needed to translate these approaches into clinical interventions.