Nature Communications (Jun 2022)

Deficiency in endocannabinoid synthase DAGLB contributes to early onset Parkinsonism and murine nigral dopaminergic neuron dysfunction

  • Zhenhua Liu,
  • Nannan Yang,
  • Jie Dong,
  • Wotu Tian,
  • Lisa Chang,
  • Jinghong Ma,
  • Jifeng Guo,
  • Jieqiong Tan,
  • Ao Dong,
  • Kaikai He,
  • Jingheng Zhou,
  • Resat Cinar,
  • Junbing Wu,
  • Armando G. Salinas,
  • Lixin Sun,
  • Mantosh Kumar,
  • Breanna T. Sullivan,
  • Braden B. Oldham,
  • Vanessa Pitz,
  • Mary B. Makarious,
  • Jinhui Ding,
  • Justin Kung,
  • Chengsong Xie,
  • Sarah L. Hawes,
  • Lupeng Wang,
  • Tao Wang,
  • Piu Chan,
  • Zhuohua Zhang,
  • Weidong Le,
  • Shengdi Chen,
  • David M. Lovinger,
  • Cornelis Blauwendraat,
  • Andrew B. Singleton,
  • Guohong Cui,
  • Yulong Li,
  • Huaibin Cai,
  • Beisha Tang

DOI
https://doi.org/10.1038/s41467-022-31168-9
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 16

Abstract

Read online

2- arachidonoylglycerol (2-AG), an abundant endocannabinoid in the brain, regulates diverse neural functions. Here, the authors identified four loss-of-function mutations in dicylglycerol lipase β (DAGLB) from six patients with early onset Parkinsonism. In mice, loss of DAGLB in dopamine neurons reduced neuronal activity and impaired locomotor function and augmentation of 2-AG levels boosted neuronal activity and rescued locomotor deficits.