![]() PARPs are classified on the basis of their ability to catalyze poly-ADP-ribosylation (PARylation) or mono-ADP-ribosylation (MARylation). The ADP ribosyltransferases (PARPs 1–17) regulate diverse cellular processes, including DNA damage repair. ![]() Despite limited clinical success to date, as we continue to refine our understanding of tau’s pathogenic mechanism(s) in different neurodegenerative diseases, we remain optimistic that tau-targeting therapies will eventually play a central role in the treatment of tauopathies. Innovative approaches to human clinical trials can help address some of the difficulties that have plagued our field’s development of tau-targeting therapies thus far. ![]() We discuss possible reasons for failures of these therapies, such as use of imperfect nonclinical models that do not predict human effects for drug development heterogeneity of human tau pathologies which may lead to variable responses to therapy and ineffective therapeutic mechanisms, such as targeting of the wrong tau species or protein epitope. We review what is known about tau biology, genetics, and therapeutic mechanisms that have been tested in clinical trials to date. However, a number of tau-targeting therapies with various mechanisms of action have shown little promise in clinical trials in different tauopathies. Multiple lines of evidence from human disease, as well as nonclinical translational models, suggest that tau has a central pathologic role in these disorders, historically thought to be primarily related to tau gain of toxic function. Here, we not only provide a new understanding of ROS/Mfn2/Akt pathway in bavachin-induced cytotoxicity via the ER stress, but also identify a new specific intervention to prevent FP-induced hepatotoxicity in the future.Tauopathies are disorders associated with tau protein dysfunction and insoluble tau accumulation in the brain at autopsy. Taken together, our study demonstrated that bavachin-induced ER stress caused cell apoptosis by Mfn2-Akt pathway, and that ROS may participate upstream in this mechanism. Additionally, suppression of reactive oxygen species (ROS) by ROS Scavenger ( N-acetyl- l-cystein (NAC)) also reduced bavachin-induced ER stress. Then, small interfering RNA (siRNA) knock-down of Mitofusion2 (Mfn2) resulted in a remarkable aggravation of ER stress through the inhibition of the phosphorylation of protein kinase B (Akt). Downregulating ER stress using tauroursodeoxycholic acid (TUDCA) obvious attenuated bavachin-triggerd cell apoptosis. Our results showed that bavachin could significantly inhibited cell proliferation and trigger the endoplasmic reticulum (ER) stress in a dose dependent manner. Bavachin, one of flavonoids in FP, has been documented as a hepatotoxic substance, and the present study aimed to determine the toxicity caused by bavachin and the possible toxic mechanisms involved using human hepatocellular carcinoma (HepG2) cells. However, its exact toxic components and mechanisms underlying remain unclear. Recently, the emerging FP-induced toxic effects, especially hepatotoxicity, in clinic are getting the public’s attention. (Fructus Psoraleae (FP)) have been widely used for the treatment of various skin diseases for hundred years. As a traditional herbal medicine, the fruits of Psoralea corylifolia L.
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