Protopanaxadiols Eliminate Behavioral Impairments and Mitochondrial Dysfunction in Parkinson's Disease Mice Model.

Currently, there are no effective therapies to cure Parkinson's disease (PD), which is the second most common neurodegenerative disease primarily characterized by motor dysfunction and degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). Protopanaxadiols (PPDs), including 20 (R)- protopanaxadiol (R-PPD) and 20 (S)- protopanaxadiol (S-PPD), are main metabolites of ginsenosides. The role of ginsenosides in neurodegenerative diseases has been thoroughly studied, however, it is unknown whether PPDs can attenuate behavioral deficits and dopaminergic neuron injury in PD model mice to date. Here, we administered PPDs to MPTP-induced PD model mice and monitored the effects on behavior and dopaminergic neurons to investigate the effects of R-PPD and S-PPD against PD. Our results showed that R-PPD and S-PPD (at a dose of 20 mg/kg, i.g.) treatment alleviated MPTP (30 mg/kg, i.p.) induced behavioral deficits. Besides, R-PPD and S-PPD protected MPP+-induced neuron injury and mitochondrial dysfunction, and reduced the abnormal expression of Cyt C, Bax, caspase-3 and Bcl-2. These findings demonstrate that R-PPD and S-PPD were potentially useful to ameliorate PD.

The Role of Calcium and Iron Homeostasis in Parkinson's Disease.

Calcium and iron are essential elements that regulate many important processes of eukaryotic cells. Failure to maintain homeostasis of calcium and iron causes cell dysfunction or even death. PD (Parkinson's disease) is the second most common neurological disorder in humans, for which there are currently no viable treatment options or effective strategies to cure and delay progression. Pathological hallmarks of PD, such as dopaminergic neuronal death and intracellular α-synuclein deposition, are closely involved in perturbations of iron and calcium homeostasis and accumulation. Here, we summarize the mechanisms by which Ca2+ signaling influences or promotes PD progression and the main mechanisms involved in ferroptosis in Parkinson's disease. Understanding the mechanisms by which calcium and iron imbalances contribute to the progression of this disease is critical to developing effective treatments to combat this devastating neurological disorder.

Palmatine Ameliorates Motor Deficits and Dopaminergic Neuron Loss by Regulating NLRP3 Inflammasome through Mitophagy in Parkinson's Disease Model Mice.

NLRP3 inflammasomes-mediated proinflammatory response and mitochondrial dysfunction play a critical role in the etiology and pathogenesis of Parkinson's disease. Negative regulation of NLRP3 inflammasome activation through mitophagy may be an important strategy to control NLRP3 inflammasome-mediated proinflammatory responses. Palmatine (PAL), an isoquinoline alkaloid found in various of plants, has potent pharmacological effects such as anti-inflammatory and anti-oxidation. However, the specific role of PAL in the pathology of Parkinson's disease remains unclear. In this study, we found that treatment with PAL improved motor deficits and reduced the loss of dopaminergic neurons in MPTP mice. Further results showed that PAL promoted mitophagy and inhibited the proinflammatory response mediated by NLRP3 inflammasomes. In addition, chloroquine (CQ, mitophagy inhibitor) attenuated the ameliorative effects of PAL on the motor deficits and dopaminergic neuron damage, as well as the inhibitory effect of PAL on NLRP3 inflammasome. Collectively, these results provide strong evidence that PAL ameliorates motor deficits and dopaminergic neuron death in Parkinson's disease, and the mechanism may be related to its inhibition of NLRP3 inflammasome activation via promoting mitophagy.