In Brain : a journal of neurology
Phospholipase C is an essential isozyme involved in the phosphoinositide signaling pathway, which maintains cellular homeostasis. Gain-of-function and loss-of-function mutations in phospholipase C impact enzymatic activity and are therefore associated with several disorders. Alternative splicing variants of phospholipase C can interfere with complex signaling networks associated with oncogenic transformation and other diseases, including brain disorders. Cells and tissues with various mutations in phospholipase C contribute different phosphoinositide signaling pathways and disease progression; however, identifying cryptic mutations in phospholipase C remains challenging. Herein, we review both the mechanisms underlying phospholipase C regulation of the phosphoinositide signaling pathway and the genetic variation of phospholipase C in several brain disorders. In addition, we discuss the present challenges associated with the potential of deep-learning-based analysis for the identification of phospholipase C mutations in brain disorders.
Lim Key-Hwan, Yang Sumin, Kim Sung-Hyun, Ko Euiseong, Kang Mingon, Joo Jae-Yeol
2022-Nov-30
PLCs, brain disorders, deep-learning, genetic variation, high-throughput analysis
