Endogenous retroviruses in neurodevelopmental, psychotic and cognitive disorders

Microbes and Infection, Год журнала: 2025, Номер unknown, С. 105479 - 105479

Опубликована: Фев. 1, 2025

Endogenous retroviruses (ERVs) are inherited retroviral genomic elements that integrated into the mammalian genome through germline infections and insertions during evolution. Human ERVs (HERVs) comprise approximately 8% of human increasingly recognized to be involved in etiology pathophysiology numerous brain disorders. In this narrative review, we summarize existing evidence linking abnormal HERV expression neurodevelopmental psychosis-related disorders discuss how these may contribute heterogeneity clinical outcomes. We also review findings suggesting aberrant late-onset cognitive with neurodegenerative components, such as Alzheimer's disease (AD) other forms dementia. conclude implicating neurodevelopmental, psychotic, is manifold stems from diverse research fields, including post-mortem studies, serological investigations, gene analyses, trials HERV-specific pharmacological compounds. The recent establishment use animal models offer a complementary experimental platform will help establish causal relationships identify specific pathways affected by expression. Yet, significant gaps persist understanding role HERVs disorders, particularly concerning specificity stability conditions. Addressing unresolved questions appears crucial for optimizing potential benefits therapeutic interventions aimed at targeting across broad spectrum HERV-associated CNS

Язык: Английский

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Recapitulation and reversal of neuropsychiatric phenotypes in a mouse model of human endogenous retrovirus type W expression

Molecular Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Март 18, 2025

Abstract Human endogenous retroviruses (HERVs) are inherited genetic elements derived from exogenous retroviral infections occurring throughout evolution. Accumulating evidence implicates increased expression of HERV type W envelope (HERV-W ENV) in psychiatric and neurodevelopmental disorders. To gain more mechanistic insights into the neurobiological disease pathways affected by HERV-W ENV expression, we took advantage a mouse model that recapitulates human-specific protein. Behavioral cognitive phenotyping transgenic (TG) mice expressing wild-type (WT) controls showed this caused deficits numerous functional domains, including repetitive behavior, social object recognition memory, sensorimotor gating. Genome-wide RNA sequencing hippocampal tissue demonstrated led to transcriptomic alterations highly relevant for disorders, functions, synaptic development. Differential gene TG encompassed downregulation several genes associated with schizophrenia autism spectrum disorder, Setd1a , Cacna1g Ank3 Shank3 as well histone methyltransferase belong Set1-like H3 lysine 4 (H3K4) family ( Kmt2a Kmt2b Kmt2d ). Concomitant latter, displayed enzymatic activity lysine-specific demethylase-1 (LSD1), H3K4 mono-methylation, decreased di- tri-methylation hippocampus. Importantly, pharmacological inhibition LSD1 through oral ORY-1001 treatment normalized abnormal methylation rescued behavioral mice. In conclusion, our study suggests has capacity disrupt various functions alter brain transcriptome manner is Moreover, identified epigenetic may offer avenues interventions against induced HERW-W expression.

Язык: Английский

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Human Endogenous RetroViruses: The iceberg view

Microbes and Infection, Год журнала: 2025, Номер unknown, С. 105530 - 105530

Опубликована: Июнь 1, 2025

Язык: Английский

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