Fig. 1

Transposable element (TE) activity in four neurological disorders: Aicardi-Goutieres Syndrome (AGS), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and Alzheimer’s Disease (AD). In AGS and MS, TE nucleic acids and endogenous retroviral (ERV) proteins may be driving inflammation through innate immune sensing pathways. In ALS and AD, the pathogenic effects of TEs appear more localized to either motor neurons (in ALS), and hippocampal or cortical neurons (in AD). Innate immune pathways are activated by double-stranded RNAs and cDNAs produced by TE/ERV transcription and reverse transcription, respectively; this is the primary mechanism implicated in AGS, and could be at play in the other disorders. In addition, envelope proteins from the HERVW and HERVK class have been shown to be neurotoxic when expressed, and implicated in MS and ALS, respectively. Increased mobilization of fully competent TEs has not been convincingly demonstrated for any neurodegenerative disorder, though this mechanism has not been fully tested