[Research progresses on PGC-1α, a key energy metabolic regulator].

Disturbance of the energy balance, when the energy intake exceeds its expenditure, is a major risk factor for the development of metabolic syndrome (MS). The peroxisome proliferator activated receptor γ (PPARγ) coactivator-1α (PGC-1α) functions as a key regulator of energy metabolism and has become a hotspot in current researches. PGC-1α sensitively responds to the environmental stimuli and nutrient signals, and further selectively binds to different transcription factors to regulate various physiological processes, including glucose metabolism, lipid metabolism, and circadian clock. In this review, we described the gene and protein structure of PGC-1α, and reviewed its tissue-specific function in the regulation of energy homeostasis in various mammalian metabolic organs, including liver, skeletal muscle and heart, etc. At the meanwhile, we summarized the application of potential small molecule compounds targeting PGC-1α in the treatment of metabolic diseases. This review will provide theoretical basis and potential drug targets for the treatment of metabolic diseases.

GABAergic inhibitory neurons as therapeutic targets for cognitive impairment in schizophrenia.

Schizophrenia is considered primarily as a cognitive disorder. However, functional outcomes in schizophrenia are limited by the lack of effective pharmacological and psychosocial interventions for cognitive impairment. GABA (gamma-aminobutyric acid) interneurons are the main inhibitory neurons in the central nervous system (CNS), and they play a critical role in a variety of pathophysiological processes including modulation of cortical and hippocampal neural circuitry and activity, cognitive function-related neural oscillations (eg, gamma oscillations) and information integration and processing. Dysfunctional GABA interneuron activity can disrupt the excitatory/inhibitory (E/I) balance in the cortex, which could represent a core pathophysiological mechanism underlying cognitive dysfunction in schizophrenia. Recent research suggests that selective modulation of the GABAergic system is a promising intervention for the treatment of schizophrenia-associated cognitive defects. In this review, we summarized evidence from postmortem and animal studies for abnormal GABAergic neurotransmission in schizophrenia, and how altered GABA interneurons could disrupt neuronal oscillations. Next, we systemically reviewed a variety of up-to-date subtype-selective agonists, antagonists, positive and negative allosteric modulators (including dual allosteric modulators) for α5/α3/α2 GABAA and GABAB receptors, and summarized their pro-cognitive effects in animal behavioral tests and clinical trials. Finally, we also discuss various representative histone deacetylases (HDAC) inhibitors that target GABA system through epigenetic modulations, GABA prodrug and presynaptic GABA transporter inhibitors. This review provides important information on current potential GABA-associated therapies and future insights for development of more effective treatments.