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Retinal detachment refers to the separation of the retinal neuroepithelium and pigment epithelium, usually involving the death of photoreceptor cells. Severe detachment may lead to permanent visual impairment if not treated properly and promptly. According to the underlying causes, retinal detachment falls into one of three categories exudative retinal detachment, traction detachment, and rhegmatogenous retinal detachment. Like many other diseases, it is difficult to study the pathophysiology of retinal detachment directly in humans, because the human retinal tissues are precious, scarce and non-regenerative; thus, establishing experimental models that better mimic the disease is necessary. In this review, we summarize the existing models of the three categories of retinal detachment both in vivo and in vitro, along with an overview of their examination methods and the major strengths and weaknesses of each model.In the past decade, there was an increasing interest in the therapeutic potential targeting ATP-sensitive potassium (KATP) channels for an effective treatment of Parkinson’s disease (PD). KATP channels are widely expressed in the central nervous system and were reported to mediate the degeneration and death of nigral dopamine neurons in the pathogenesis of PD. This review aims to address the pivotal roles of KATP channels played in the mechanisms underlying PD pathogenesis, and provide possible directions for further research from different perspectives, such as the vulnerability of dopamine neurons in the substantia nigra, neurotransmitter releasing, iron metabolism in the brain, α-synuclein secretion and mitochondrial dysfunction, which are off critical importance in the investigation of KATP channels-targeted precise therapeutic interventions for PD.Brain derived neurotrophic factor (BDNF) promotes maturation of dopaminergic (DAergic) neurons in the midbrain and positively regulates their maintenance and outgrowth. Therefore, understanding the mechanisms regulating the BDNF signaling pathway in DAergic neurons may help discover potential therapeutic strategies for neuropsychological disorders associated with dysregulation of DAergic neurotransmission. Because estrogen-related receptor gamma (ERRγ) is highly expressed in both the fetal nervous system and adult brains during DAergic neuronal differentiation, and it is involved in regulating the DAergic neuronal phenotype, we asked in this study whether ERRγ ligand regulates BDNF signaling and subsequent DAergic neuronal phenotype. Based on the X-ray crystal structures of the ligand binding domain of ERRγ, we designed and synthesized the ERRγ agonist, (E)-4-hydroxy-N’-(4-(phenylethynyl)benzylidene)benzohydrazide (HPB2) (Kd value, 8.35 μmol/L). HPB2 increased BDNF mRNA and protein levels, and enhanced the exphenotype in neuronal cells. Our results might provide new insights into the mechanism underlying the regulation of BDNF expression, leading to novel therapeutic strategies for neuropsychological disorders associated with DAergic dysregulation.Short-chain fatty acids (SCFAs), mainly including acetate, propionate, and butyrate, are metabolites produced during the bacterial fermentation of dietary fiber in the intestinal tract. They are believed to be essential factors affecting host health. Most in vitro and ex vivo studies have shown that SCFAs affect the regulation of inflammation, carcinogenesis, intestinal barrier function, and oxidative stress, but convincing evidence in humans is still lacking. Two major SCFA signaling mechanisms have been identified promotion of histone acetylation and activation of G-protein-coupled receptors. In this review, we introduce the production and metabolic characteristics of SCFAs, summarize the potential effects of SCFAs on the four aspects mentioned above and the possible mechanisms. SCFAs have been reported to exert a wide spectrum of positive effects and have a high potential for therapeutic use in human-related diseases.Because dysregulation of protein kinases owing to mutations or overexpression plays causal roles in human diseases, this family of enzymes has become one of the most important drug targets of the 21st century. Of the 62 protein kinases inhibitors that are approved by the FDA, seven of them form irreversible covalent adducts with their target enzymes. The clinical success of ibrutinib, an inhibitor of Bruton tyrosine kinase, in the treatment of mantle cell lymphomas following its approval in 2013 helped to overcome a general bias against the development of irreversible drug inhibitors. The other approved covalent drugs include acalabrutinib and zanubrutinib, which also inhibit Bruton tyrosine kinase. Furthermore afatinib, dacomitinib, and osimertinib, inhibitors of members of the epidermal growth factor receptor family (ErbB1/2/3/4), are used in the treatment of non-small cell lung cancers. Neratinib is an inhibitor of ErbB2 and is used in the treatment of ErbB2/HER2-positive breast cancer. The seven drugs convoided to become an emerging paradigm. Much of this recent success can be attributed to the clinical efficacy of ibrutinib as well as the other antagonists covered in this review. Moreover, the covalent inhibitor methodology is swiftly gaining acceptance as a valuable component of the medicinal chemist’s toolbox and is primed to make a significant impact on the development of enzyme antagonists and receptor modulators.Neuronal regeneration in the injured central nervous system is hampered by multiple extracellular proteins. These proteins exert their inhibitory action through interactions with receptors that are located in cholesterol rich compartments of the membrane termed lipid rafts. Here we show that cholesterol-synthesis inhibition prevents the association of the Neogenin receptor with lipid rafts. Furthermore, we show that cholesterol-synthesis inhibition enhances axonal growth both on inhibitory -myelin and -RGMa substrates. Following optic nerve injury, lowering cholesterol synthesis with both drugs and siRNA-strategies allows for robust axonal regeneration and promotes neuronal survival. SM04690 order Cholesterol inhibition also enhanced photoreceptor survival in a model of Retinitis Pigmentosa. Our data reveal that Lovastatin leads to several opposing effects on regenerating axons cholesterol synthesis inhibition promotes regeneration whereas altered prenylation impairs regeneration. We also show that the lactone prodrug form of lovastatin has differing effects on regeneration when compared to the ring-open hydroxy-acid form.