Ddc-flox Mouse

Ddc, also known as aromatic-l-amino-acid decarboxylase (AADC), is an enzyme that converts L-Dopa to dopamine [2]. Dopamine is a significant signaling molecule in the neuroendocrine system [3]. Ddc is thus crucial for dopamine synthesis, which is involved in numerous biological processes including neurotransmission, and is of great biological importance. Genetic models can be valuable for studying its functions.

In Parkinson's disease research, due to the relative sparing of Ddc expression while tyrosine hydroxylase (TH) expression is reduced in the substantia nigra pars compacta (SNpc), Ddc-positive neurons may be a therapeutic target. An AAV vector with a rat Ddc promoter was developed to target Ddc-positive neurons in the SNpc. Chemogenetic activation of these neurons in an A53T-mutated alpha-synuclein overexpression model of PD alleviated parkinsonian motor symptoms and rescued nigrostriatal TH expression, suggesting a potential therapeutic strategy for PD [1]. Also, in Procambarus clarkii, knocking down Pc-ddc led to changes in dopamine receptor (Pc-dar) expression, endogenous Pc-DDC enzymatic activities, and activation of the Toll (TLRs) signaling pathway and ROS-related antioxidant enzyme genes after bacterial challenge, indicating that Ddc and its related receptor play mediating roles in the antibacterial innate immune reactions of the hepatopancreas [3].

In conclusion, Ddc is essential for dopamine synthesis, playing key roles in neurotransmission and the neuroendocrine-immune system. In the context of Parkinson's disease, Ddc-positive neurons could potentially be a therapeutic target. The findings from model-based research, such as the use of A53T-mutated alpha-synuclein overexpression model in PD and RNAi assay in Procambarus clarkii, have provided insights into Ddc's functions in disease conditions and biological processes.