Backgrounds: Numerous lines of evidence support the intricate interplay between Parkinson's disease (PD) and the PINK1-dependent mitophagy process. This study aimed to evaluate differences in plasma PINK1 levels among idiopathic PD, PD syndromes (PDs), and healthy controls. Methods: A total of 354 participants were included, consisting of 197 PD patients, 50 PDs patients, and 107 healthy controls were divided into two cohorts, namely the modeling cohort (cohort 1) and the validated cohort (cohort 2). An enzyme-linked immunosorbent assay (ELISA)-based analysis was performed on PINK1 and α-synuclein oligomer (Asy-no). The utilization of the area under the curve (AUC) within the receiver-operating characteristic (ROC) curves served as a robust and comprehensive approach to evaluate and quantify the predictive efficacy of plasma biomarkers alone, as well as combined models, in distinguishing PD patients from controls. Results: PINK1 and Asy-no were elevated in the plasma of PD and PDs patients compared to healthy controls. The AUCs of PINK1 (0.771) and Asy-no (0.787) were supposed to be potentially eligible plasma biomarkers differentiating PD from controls but could not differentiate PD from PDs. Notably, the PINK + Asy-no + Clinical RBD model showed the highest performance in the modeling cohort and was comparable with the PINK1 + Clinical RBD in the validation cohort. Moreover, there is no significant correlation between PINK1 and UPDRS, MMSE, HAMD, HAMA, RBDQ-HK, and ADL scores. Conclusion: These findings suggest that elevated PINK1 in plasma holds the potential to serve as a non-invasive tool for distinguishing PD patients from controls. Moreover, the outcomes of our investigation lend support to the plausibility of implementing a feasible blood test in future clinical translation.
The cell membrane structure is closely related to the occurrence and progression of many metabolic bone diseases observed in the clinic and is an important target to the development of therapeutic strategies for these diseases. Strong experimental evidence supports the existence of membrane microdomains in osteoclasts (OCs). However, the potential membrane microdomains and the crucial mechanisms underlying their roles in OCs have not been fully characterized. Membrane microdomain components, such as scaffolding proteins and the actin cytoskeleton, as well as the roles of individual membrane proteins, need to be elucidated. In this review, we discuss the compositions and critical functions of membrane microdomains that determine the biological behavior of OCs through the three main stages of the OC life cycle.
Membrane Proteins , Osteoclasts , Membrane Proteins/metabolism , Membrane Microdomains/metabolism , Cell Membrane Structures/metabolism
Osteoporosis a common disease in postmenopausal women which contains significant impact on the living quality of women. With the aging of the population, the number of patients suffer from osteoporosis has shown a significant increase. Given the limitations of clinical drugs for the treatment of osteoporosis, natural extracts with small side effects have a great application prospect in the treatment of osteoporosis. Praeruptorin B (Pra-B), is one of the main components found in the roots of Peucedanum praeruptorum Dunn and exhibits anti-inflammatory effects. However, there is no research on the influence of Pra-B on osteoporosis. Here, we showed that Pra-B can dose-dependently suppress osteoclastogenesis without cytotoxicity. Receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL)-induced the nuclear import of P65 was inhibited by Pra-B, which indicated the suppressive effect of Pra-B on NF-κB signaling. Further, Pra-B enhanced the expression of Glutathione S-transferase Pi 1 (GSTP1) and promoted the S-glutathionylation of IKKß to inhibit the nuclear translocation of P65. Moreover, in vivo experiments showed that Pra-B considerably attenuated the bone loss in ovariectomy (OVX)-induced mice. Collectively, our studies revealed that Pra-B suppress the NF-κB signaling targeting GSTP1 to rescued RANKL-induced osteoclastogenesis in vitro and OVX-induced bone loss in vivo, supporting the potential of Pra-B for treating osteoporosis in the future.
I-kappa B Kinase , Osteoporosis , Animals , Cell Differentiation , Coumarins , Female , Glutathione S-Transferase pi/metabolism , Humans , I-kappa B Kinase/metabolism , Mice , NF-kappa B/metabolism , Osteoclasts , Osteogenesis , Osteoporosis/metabolism , Ovariectomy , RANK Ligand/metabolism , RANK Ligand/pharmacology
The incidence of osteoporosis, which is primarily characterized by plethoric osteoclast (OC) formation and severe bone loss, has increased in recent years. Millions of people worldwide, especially postmenopausal women, suffer from osteoporosis. The drugs commonly used to treat osteoporosis still exist many disadvantages, but natural extracts provide options for the treatment of osteoporosis. Therefore, the identification of cost-effective natural compounds is important. Patchouli alcohol (PA), a natural compound extracted from Pogostemon cablin that exerts anti-inflammatory effects, is used as a treatment for gastroenteritis. However, no research on the use of Patchouli alcohol in osteoporosis has been reported. We found that PA dose-dependently inhibited the receptor activator of nuclear factor kappa-B ligand (RANKL)-induced formation and function of OCs without cytotoxicity. Furthermore, these inhibitory effects were reflected in the significant effect of PA on the NF-κB signaling pathway, as PA suppressed the transcription factors NFATc1 and c-Fos. We also determined that PA activated expression of the nuclear receptor pregnane X receptor (PXR) and promoted the PXR/Toll-like receptor 4 (TLR4) axis to inhibit the nuclear import of NF-κB (p50 and p65). Additionally, PA exerted therapeutic effects against osteoporosis in ovariectomized (OVX) mice, supporting the use of PA as a treatment for osteoporosis in the future.
