Parkinson’s disease, the second major neurodegenerative disease, has created a great impact on the elder people. Although the mechanisms underlying Parkinson’s disease are not fully understood, considerable evidence suggests that neuro-inflammation, oxidative stress, mitochondrial dysfunction, cell proliferation, differentiation and apoptosis are involved in the disease. p38MAPK, an important member of the mitogen-activated protein family, controls several important functions in the cell, suggesting a potential pathogenic role in PD. This review provides a brief description of the role and mechanism of p38MAPK in Parkinson’s disease.

Millions of people suffer from Alzheimer's disease (AD) and Parkinson's disease (PD) worldwide. Due to their complex pathology, no effective pharmacological treatment has been found to date, despite extensive research. Developing new, effective therapeutic agents to cure these disease remains a major challenge. Although the cause of AD and PD remains illusive, numerous studies indicates that oxidative stress and neuro-inflammation lead to neurodegeneration in the central nervous system and play vital role in AD and PD morbidity and progression. Flavonoids, which are found widely in nature, exhibit anti-oxidative, anti-inflammatory, anti-mutative, anti-microbial, and neuroprotective properties, so have potential to treat these two kinds of diseases. In this review, we focus on the anti-oxidative and neuroprotective action of flavonoids in attenuating Alzheimer's and Parkinson's disease, and how they might be harnessed in the development of new pharmacological agents to treat these two diseases. Some flavonoid compounds, like hesperidin, naringin, naringenin, tangeretin, nobiletin, silibinin, Epigallocatechin-3-gallate, displayed to be effective in both AD and PD. Considerable studies have demonstrated the anti-AD and anti-PD effects of flavonoids through various in vitro and in vivo models. However, more rigorous studies are needed to be done for flavonoids to develop into effective drugs and apply them to clinical practice.

Major depressive disorder (MDD) is one of the most common mental health conditions, characterized by pervasive and persistent low mood, low self-esteem, and a loss of interest or pleasure in activities that are typically enjoyable. Despite decades of research into the etiology and pathophysiological mechanisms of depression, the therapeutic outcomes for many individuals remain less than expected. A promising new area of research focuses on stress-induced neuroinflammatory processes, such as the excessive activation and crosstalk of microglia and astrocytes in the central nervous system under stress, as well as elevated levels of pro-inflammatory cytokines, which are closely linked to the onset and progression of depression. This review summarizes the mechanisms through which neuroinflammation induces or promotes the development of depression, and also highlights the effective roles of small molecules with anti-inflammatory activity in the treatment of MDD. Understanding the specific mechanisms through which stress-induced neuroinflammation further impacts depression, and using technologies such as single-cell RNA sequencing to elucidate the specific subtypes and interactions of microglia and astrocytes in depression, is of great importance for developing more effective therapeutic strategies for MDD.

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.

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.