bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: April 23, 2025
Abstract The diacylglycerol lipases, DAGLα and DAGLβ, hydrolyse (DAG) to produce 2-arachidonoylglycerol (2-AG), a key endocannabinoid (eCB) CB 1 /CB 2 receptor ligand. While is well established as regulator of -dependent synaptic plasticity, recent studies have identified DAGLB mutations cause autosomal recessive early-onset Parkinson’s disease (PD). Here, we present comprehensive analysis DAGLβ mRNA expression, demonstrating its co-expression with predominantly in excitatory neurons throughout the adult nervous system. We see no evidence for enrichment DAGLs or transcripts striatum dopaminergic neurons. discuss these findings within review literature that points wider involvement eCB system PD. Notably, DAGLα-dependent 2-AG release at synapses relies on α-synuclein function—a protein central PD pathophysiology—implicating both pointing widespread disruption release. Consistent this, substantial reductions levels been reported cerebrospinal fluid (CSF) patients. Depression, major non-motor symptom PD, often precedes onset motor deficits by several years. Human mouse genetic suggest reduced DAGL activity may contribute depression impairing 2-AG-mediated signalling, which crucial stress resilience, mood regulation. These point potential causal link between dysfunction symptoms
Language: Английский