Parkinson's Disease (PD) is a neurodegenerative disorder characterized by the pathological accumulation of alpha-synuclein (α-syn) in the neuronal cell bodies of the substantia nigra. The glymphatic system within the Central Nervous System (CNS) is responsible for clearing metabolic waste and abnormal proteins and its dysfunction may significantly contribute to the pathogenesis of PD. Our previous study showed that OAB-14, the novel small molecular compound, showed a great potential effect in APP/PS1 transgenic mice. Given the similarities in the pathogenesis of PD and Alzheimer's disease (AD), it is pertinent to explore the therapeutic potential of OAB-14 in the context of PD. This study utilized a rotenone-induced PD mice model to evaluate the effects of oral administration of OAB-14, and its underlying mechanisms. Here we confirmed the neuroprotective effect and motor improvement of OAB-14 in rotenone-induced PD model mice. Our research has shown that OAB-14 is capable of enhancing the glymphatic system function by promoting the influx and efflux of the CSF tracers to the brain and deep cervical lymph nodes, respectively, to promote the clearance of α-syn. In addition, OAB-14 could down-regulate MyD88, NF-kB (Ser 536) phosphorylation, and TLR4 to reduce glial cell activation; and down-regulate cleaved-caspase1, NLRP3, ASC, IL-1β, IL-6, IL-18, TNF-α, and IL-10 to reduce the expression of inflammatory vesicles and pro-inflammatory factors, and to reduce neuronal oxidative stress. In summary, OAB-14 may promote the clearance of brain α-syn through the glial lymphatic system, inhibit the α-syn/TLR4/NF-κB/NLRP3 inflammatory pathway, and improve movement disorders.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), abnormal accumulation of α-synuclein (α-syn), and activation of microglia leading to neuroinflammation. Disturbances in circadian rhythm play a significant role in PD, with most non-motor symptoms associated with disruptions in circadian rhythm. These disturbances can be observed years before motor symptoms appear and are marked by the emergence of non-motor symptoms related to PD, such as rapid eye movement sleep behavior disorder (RBD), restless leg syndrome (RLS), excessive daytime sleepiness (EDS), depression and anxiety, changes in blood pressure, gastrointestinal dysfunction, and urinary problems. Circadian rhythm disruption precedes the onset of motor symptoms and contributes to the progression of PD. In brief, this article outlines the role of circadian rhythm disruption in triggering PD at cellular and molecular levels, as well as its clinical manifestations. It also explores how circadian rhythm research can contribute to preventing the onset and progression of PD from current and future perspectives.

For nearly three decades, more than 80 embryonic stem cell lines and more than 100 induced pluripotent stem cell lines have been derived from New World monkeys, Old World monkeys, and great apes. In this comprehensive review, we examine these cell lines originating from marmoset, cynomolgus macaque, rhesus macaque, pig-tailed macaque, Japanese macaque, African green monkey, baboon, chimpanzee, bonobo, gorilla, and orangutan. We outline the methodologies implemented for their establishment, the culture protocols for their long-term maintenance, and their basic molecular characterization. Further, we spotlight any cell lines that express fluorescent reporters. Additionally, we compare these cell lines with human pluripotent stem cell lines, and we discuss cell lines reprogrammed into a pluripotent naive state, detailing the processes used to attain this. Last, we present the findings from the application of these cell lines in two emerging fields: intra- and interspecies embryonic chimeras and blastoids.

Although striatal delivery of three critical genes for dopamine synthesis by viruses is a potential clinical approach for treating Parkinson's disease (PD), the approach makes it difficult to finely control dopamine secretion amounts and brings safety concerns. Here, we generate genetically engineered mesenchymal stem cells encoding three critical genes for dopamine synthesis (DOPA-MSCs). DOPA-MSCs retain their MSC identity and stable ability to secrete dopamine during passaging. Following transplantation, DOPA-MSCs reinstate striatal dopamine levels and correct motor function in PD rats. Importantly, after grafting into the caudate and putamen, DOPA-MSCs provide homotopic reconstruction of midbrain dopamine pathways by restoring striatal dopamine levels, and safely and long-term (up to 51 months) correct motor disorders and nonmotor deficits in acute and chronic PD rhesus monkey models of PD even with advanced PD symptoms. The long-term benefits and safety results support the idea that the development of dopamine-synthesized engineered cell transplantation is an important strategy for treating PD.

Glioma is characterized as the most aggressive brain tumor that occurred in the central nervous system. The circadian rhythm is an essential cyclic change system generated by the endogenous circadian clock. Current studies found that the circadian clock affects glioma pathophysiology. It is still controversial whether the circadian rhythm disruption is a cause or an effect of tumorigenesis. This review discussed the association between cell cycle and circadian clock and provided a prominent molecular theoretical basis for tumor therapy. We illustrated the external factors affecting the circadian clock including thermodynamics, hypoxia, post-translation, and microRNA, while the internal characteristics concerning the circadian clock in glioma involve stemness, metabolism, radiotherapy sensitivity, and chemotherapy sensitivity. We also summarized the molecular pathways and the therapeutic drugs involved in the glioma circadian rhythm. There are still many questions in this field waiting for further investigation. The results of glioma chronotherapy in sensitizing radiation therapy and chemotherapy have shown great therapeutic potential in improving clinical outcomes. These findings will help us further understand the characteristics of glioma pathophysiology.