Lindberg D, Shan D, Ayers-Ringler J, Oliveros A, Benitez J, Prieto M, McCullumsmith R, Choi D-S
Neurobiology of Disease Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Curr Mol Med. 2015;15(3):275-95. doi: 10.2174/1566524015666150330163724.
Purinergic signaling regulates numerous vital biological processes in the central nervous system (CNS). The two principle purines, ATP and adenosine act as excitatory and inhibitory neurotransmitters, respectively. Compared to other classical neurotransmitters, the role of purinergic signaling in psychiatric disorders is not well understood or appreciated. Because ATP exerts its main effect on energy homeostasis, neuronal function of ATP has been underestimated. Similarly, adenosine is primarily appreciated as a precursor of nucleotide synthesis during active cell growth and division. However, recent findings suggest that purinergic signaling may explain how neuronal activity is associated neuronal energy charge and energy homeostasis, especially in mental disorders. In this review, we provide an overview of the synaptic function of mitochondria and purines in neuromodulation, synaptic plasticity, and neuron-glia interactions. We summarize how mitochondrial and purinergic dysfunction contribute to mental illnesses such as schizophrenia, bipolar disorder, autism spectrum disorder (ASD), depression, and addiction. Finally, we discuss future implications regarding the pharmacological targeting of mitochondrial and purinergic function for the treatment of psychiatric disorders.
嘌呤能信号传导调节中枢神经系统（CNS）中的众多重要生物学过程。两种主要嘌呤，即ATP和腺苷分别作为兴奋性和抑制性神经递质发挥作用。与其他经典神经递质相比，嘌呤能信号传导在精神疾病中的作用尚未得到充分理解或重视。由于ATP主要对能量稳态发挥作用，其神经元功能一直被低估。同样，腺苷主要被视为活跃细胞生长和分裂过程中核苷酸合成的前体。然而，最近的研究结果表明，嘌呤能信号传导可能解释神经元活动如何与神经元能量电荷和能量稳态相关联，尤其是在精神疾病中。在本综述中，我们概述了线粒体和嘌呤在神经调节、突触可塑性和神经元-胶质细胞相互作用中的突触功能。我们总结了线粒体和嘌呤能功能障碍如何导致精神疾病，如精神分裂症、双相情感障碍、自闭症谱系障碍（ASD）、抑郁症和成瘾。最后，我们讨论了针对线粒体和嘌呤能功能进行药物靶向治疗精神疾病的未来意义。
