Interferons (IFNs) bind to cell surface receptors and activate the expression of interferon-stimulated genes (ISGs) through intracellular signaling cascades. ISGs and their expression products have various biological functions, such as antiviral and immunomodulatory effects, and are essential effector molecules for IFN function. ISGs limit the invasion and replication of the virus in a cell-specific and region-specific manner in the central nervous system (CNS). In addition to participating in natural immunity against viral infections, studies have shown that ISGs are essential in the pathogenesis of CNS disorders such as neuroinflammation and neurodegenerative diseases. The aim of this review is to present a macroscopic overview of the characteristics of ISGs that restrict viral neural invasion and the expression of the ISGs underlying viral infection of CNS cells. Furthermore, we elucidate the characteristics of ISGs expression in neurological inflammation, neuropsychiatric disorders such as depression as well as neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). Finally, we summarize several ISGs (ISG15, IFIT2, IFITM3) that have been studied more in recent years for their antiviral infection in the CNS and their research progress in neurological diseases.

Type II deiodinase (DIO2) is thought to provide triiodothyronine (T3) to the nucleus to meet intracellular needs by deiodinating the prohormone thyroxine. DIO2 is expressed widely in many tissues and plays an important role in a variety of physiological processes, such as controlling T3 content in developing tissues (e.g., bone, muscles, and skin) and the adult brain, and regulating adaptive thermogenesis in brown adipose tissue (BAT). However, the identification and cloning of DIO2 have been challenging. In recent years, several clinical investigations have focused on the Thr92Ala polymorphism, which is closely correlated with clinical syndromes such as type 2 diabetes, obesity, hypertension, and osteoarthritis. Thr92Ala-DIO2 was also found to be related to bone and neurodegenerative diseases and tumors. However, relatively few reviews have synthesized research on individual deiodinases, especially DIO2, in the past 5 years. This review summarizes current knowledge regarding the physiological functions of DIO2 in thyroid hormone signaling and adaptive thermogenesis in BAT and the brain, as well as the associations between Thr92Ala-DIO2 and bone and neurodegenerative diseases and tumors. This discussion is expected to provide insights into the physiological functions of DIO2 and the clinical syndromes associated with Thr92Ala-DIO2.

Spinal cord injury (SCI) is a central nervous system (CNS) disease that can cause sensory and motor impairment below the level of injury. Currently, the treatment scheme for SCI mainly focuses on secondary injury and complications. Recent studies have shown that SCI leads to an imbalance of intestinal microbiota and the imbalance is also associated with complications after SCI, possibly through the microbial-brain-gut axis. Melatonin is secreted in many parts of the body including pineal gland and gut, effectively protecting the spinal cord from secondary damage. The secretion of melatonin is affected by circadian rhythms, known as the dark light cycle, and SCI would also cause dysregulation of melatonin secretion. In addition, melatonin is closely related to the intestinal microbiota, which protects the barrier function of the gut through its antioxidant and anti-inflammatory effects, and increases the abundance of intestinal microbiota by influencing the metabolism of the intestinal microbiota. Furthermore, the intestinal microbiota can influence melatonin formation by regulating tryptophan and serotonin metabolism. This paper summarizes and reviews the knowledge on the relationship among intestinal microbiota, melatonin, and SCI in recent years, to provide new theories and ideas for clinical research related to SCI treatment.

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the formation of amyloid plaques, neurofibrillary tangles and progressive cognitive decline. Amyloid-beta peptide (Aβ) monoclonal antibody therapeutic clinical trials have nearly failed, raising significant concerns about other etiological hypotheses about AD. Recent evidence suggests that AD patients also exhibit persistent neuronal loss and neuronal death accompanied by brain iron deposition or overload-related oxidative stress. Ferroptosis is a type of cell death that depends on iron, unlike autophagy and apoptosis. Inhibiting neuronal ferroptosis function is effective in improving cognitive impairment in AD. Notably, new research shows that ferroptosis in AD is crucially dependent on glial cell activation. This review examines the relationship between the imbalance of iron metabolism, the regulation of iron homeostasis in glial cells and neuronal death in AD pathology. Finally, the review summarizes some current drug research in AD targeting iron homeostasis, many novel iron-chelating compounds and natural compounds showing potential AD-modifying properties that may provide therapeutic targets for treating AD.

Protein tyrosine phosphatase receptor type J (PTPRJ), also known as DEP-1, HPTPη, or CD148, belongs to the R3 subfamily of receptor protein tyrosine phosphatases (RPTPs). It was first identified as an antioncogene due to its protein level being significantly downregulated in most epithelial tumors and cancer cell lines (e.g., colon, lung, thyroid, breast, and pancreas). PTPRJ regulates mouse optic nerve projection by inhibiting the phosphorylation of the erythropoietin-producing hepatocellular carcinoma (Eph) receptor and abelson murine leukemia viral oncogene homolog 1 (c-Abl). PTPRJ is crucial for metabolism. Recent studies have demonstrated that PTPRJ dephosphorylates JAK2 at positions Y813 and Y868 to inhibit leptin signaling. Akt is more phosphorylated at the Ser473 and Thr308 sites in Ptprj^−/− mice, suggesting that PTPRJ may be a novel negative regulator of insulin signaling. PTPRJ also plays an important role in balancing the pro- and anti-osteoclastogenic activity of the M-CSF receptor (M-CSFR), and in maintaining NFATc1 expression during the late stages of osteoclastogenesis to promote bone-resorbing osteoclast (OCL) maturation. Furthermore, multiple receptor tyrosine kinases (RTKs) as substrates of PTPRJ are probably a potential therapeutic target for many types of diseases, such as cancer, neurodegenerative diseases, and metabolic diseases, by inhibiting their phosphorylation activity. In light of the important roles that PTPRJ plays in many diseases, this review summarizes the structural features of the protein, its expression pattern, and the physiological and pathological functions of PTPRJ, to provide new ideas for treating PTPRJ as a potential therapeutic target for related metabolic diseases and cancer.