GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE306nnn/GSE306116/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306116GEOGSEfalseCaspase-3 Control of RNA Splicing and Mitochondrial Dynamics in Microglia during Parkinson’s Disease [RNA-Seq]Caspase-3, a cysteine-aspartic protease canonically known for its role in apoptotic cell death, has been implicated in several non-apoptotic functions, particularly in microglia, the brain-resident macrophages. These novel functions appear to depend on distinct levels of caspase-3 activation; however, the role of basal caspase-3 activity remains unclear. Here, we show that basal caspase-3 regulates RNA splicing in microglia, and its inhibition in a Parkinson´s disease (PD) model leads to splicing dysregulation. Loss of basal caspase-3 activity also increases double-stranded RNA (dsRNA) accumulation, inducing a type I interferon response. Additionally, caspase-3 deficiency impairs mitochondrial respiration, reduces ATP production, and causes sex-specific mitochondrial abnormalities, predominantly in female microglia. Together, our findings uncover a non-apoptotic, homeostatic role for basal caspase-3 activity in microglia. Its disruption, such as in PD, may drive key molecular features of neuroinflammation and neurodegeneration, positioning caspase-3 as a critical regulator of microglial function in health and disease.2026/08/06GSE306116GSM9193477GSM9193478GSM9193479GSM9686322GSM9686323GSM9686324GSM9686325GSM9686326GSM9686327GSM9193480GSM9193481GSM91934823017224247306116Mus musculus