Nuclear speckles in neurodegeneration
Nuclear speckles are dynamic nuclear condensates that coordinate RNA metabolism, transcription, chromatin organization, and cellular stress responses.
Through dynamic remodeling under diverse stress conditions, nuclear speckles serve as pivotal hubs of proteostasis and neuronal resilience, orchestrating the unfolded protein response, heat shock response, and DNA damage response.
In neurodegenerative proteinopathies, misfolded proteins, including tau and Chromosome 9 Open Reading Frame 72-amyotrophic lateral sclerosis (C9ORF72-ALS)-associated dipeptide repeats, disrupt nuclear speckle integrity, driving transcriptional and splicing impairments that compromise neuronal survival.
Emerging therapeutic strategies, including pharmacological ‘rejuvenation’ of nuclear speckles, highlight the potential of nuclear speckles as actionable targets for restoring homeostasis and mitigating proteinopathies.
https://www.cell.com/trends/neurosciences/fulltext/S0166-2236(26)00013-5
