N6-methyladenosine (m6A) is a ubiquitous mRNA modification in eukaryotes. m6A occurs through the action of methyltransferases, demethylases, and methylation-binding proteins. m6A methylation of RNA is associated with various neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), depression, cerebral apoplexy, brain injury, epilepsy, cerebral arteriovenous malformations, and glioma. Furthermore, recent studies report that m6A-related drugs have attracted considerable concerns in the therapeutic areas of neurological disorders. Here, we mainly summarized the role of m6A modification in neurological diseases and the therapeutic potential of m6A-related drugs. The aim of this review is expected to be useful to systematically assess m6A as a new potential biomarker and develop innovative modulators of m6A for the amelioration and treatment of neurological disorders.

Alzheimer's disease (AD) remains a medical and social challenge worldwide. Magnesium (Mg) is one of the most frequently evaluated essential minerals with diverse biological functions in human body. However, the association between circulating Mg levels and AD remains controversial. We conducted a meta-analysis of 21 studies published between 1991 and 2021 to determine whether the Mg levels in the blood and cerebrospinal fluid (CSF) are abnormal in AD. Literatures were searched in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data without language limitations. A pooled subject sample including 1,112 AD patients and 1,001 healthy controls (HCs) was available to assess Mg levels in serum and plasma; 284 AD patients and 117 HCs were included for Mg levels in CSF. It was found that serum and plasma levels of Mg were significantly reduced in AD patients compared with HCs (standardized mean difference [SMD] = −0.89; 95% confidence interval [CI] [−1.36, −0.43];P= 0.000). There was statistically non-significant for Mg level in CSF between AD and HCs, whereas a decreased tendency were detected (SMD = −0.16; 95% CI [−0.50, 0.18];P= 0.364). .In addition, when we analyzed the Mg levels of serum, plasma and CSF together, the circulating Mg levels in AD patients was significantly lower (SMD = −0.74, 95% CI [−1.13; −0.35];P= 0.000). These results indicate that Mg deficiency may be a risk factor of AD and Mg supplementation may be a potentially valuable adjunctive treatment for AD.Systematic Review Registration:www.crd.york.ac.uk/PROSPERO/, registration number CRD42021254557.

Fibroblast Growth Factors and Fibroblast Growth Factor Receptors (FGFs/FGFRs) constitute a complex and diverse signaling system crucial in various biological processes, such as cell proliferation, differentiation, migration, and survival. Dysregulation of the FGFs/FGFRs system plays a key role in the progression of neurological diseases through the neuroinflammatory process. FGFs/FGFRs have become a key target of novel drugs in recent years for the treatment of neurological diseases. Notably, drug delivery systems can enhance the clinical therapeutic efficacy of these drugs. This review highlights the critical role of FGFs/FGFRs in various neuroinflammatory diseases and provides an overview of the current research on FGFs/FGFRs-targeted therapeutic drugs, their novel delivery systems, and development potential. Advances in this field can enhance further application of potential drugs, offering new insights and approaches for treating neuroinflammatory diseases, thus reducing the incidence and progression. Moreover, this review summarizes the structure and function of FGFs/FGFRs, elucidates the signaling pathways through which the FGFs/FGFRs system is involved in neuroinflammatory diseases (Alzheimer's disease (AD) and Parkinson's disease (PD)), and emphasizes the key role of FGFs/FGFRs system in disease progression. Furthermore, the current anti-inflammatory drugs targeting the FGFs/FGFRs system, including direct FGF modulators and indirect FGF modulators, have been summarized. The positive impact of the development of novel drug delivery systems, such as liposomes, microspheres, and hydrogels, on therapeutic outcomes has also been discussed. Therefore, this review may offer guidance and insights for the management of neuroinflammatory disorders.

Phagocytosis is a core function of immune cells in the central nervous system (CNS), primarily executed by brain macrophages. This cellular ensemble comprises microglia, border-associated macrophages (BAMs), and peripherally recruited blood-derived macrophages, which collectively regulate brain development, homeostasis maintenance, and disease progression. During the progression of CNS diseases, brain macrophages exhibit dual roles in phagocytic function. Moderate phagocytosis exerts neuroprotective effects, whereas excessive phagocytosis impairs normal neural structures. The underlying regulatory mechanisms are highly complex. Notably, key receptors involved in phagocytosis represent potential therapeutic targets for CNS diseases, and various drugs targeting these receptors to modulate brain macrophage function have demonstrated promising therapeutic potential. In recent years, the emergence of novel drug delivery systems has exerted a positive impact on the clinical translation of such drugs. Nevertheless, systematic summaries of relevant research progress remain lacking. The present review comprehensively elaborates on the physiological functions of brain macrophages, with a primary focus on the regulatory pathways of phagocytosis and their therapeutic value in CNS diseases. It also summarizes strategies for targeted modulation of phagocytic function using natural products, synthetic drugs and biological agents, while exploring the role of advanced delivery systems, including nanogels, liposomes, nanoparticles, nanovesicles, and supramolecular inclusion complexes, in enhancing therapeutic efficacy. Collectively, this review intends to provide a theoretical basis and directional guidance for optimizing therapeutic strategies targeting the phagocytic function of brain macrophages in CNS diseases and advancing the development of novel drug delivery systems.

Microglia (MG) play dual roles in Alzheimer’s disease (AD) development. They can worsen the condition by causing inflammation but also help in early stages by removing harmful amyloid-beta (Aβ) through phagocytosis. Consequently, precise modulation of microglial phagocytic activity and inflammatory responses holds considerable significance for AD treatment. Cordycepin (Cor) is a representative active component extracted from Cordyceps militaris, which is a type of medicinal and nutritional food. Although Cor is considered to exert neuroprotective effects, its potential regulatory role in microglial function in AD, as well as the underlying specific mechanisms, remain poorly elucidated. Through transcriptomics combined with in vitro and in vivo experimental validations, we demonstrated that Cor suppresses the pro-inflammatory responses of MG while enhancing their phagocytic capacity for Aβ, with these dual effects mediated through distinct mechanisms. Specifically, on one hand, Cor can activate the STAT6 signaling pathway to upregulate the expression of phagocytosis-related factors, including Arg1, TGFβ, IL10, and CD206, thereby promoting the clearance of Aβ by MG. Notably, activation of the STAT6 signaling pathway does not affect the inflammatory response. On the other hand, Cor can inhibit caspase1 to reduce the levels of inflammation-related factors such as IL1β, TNFα, iNOS, and CD86, thereby alleviating neuroinflammation. Meanwhile, inhibition of caspase1 activity does not impact phagocytic function. This unique dual action of Cor, which simultaneously suppresses inflammation and promotes phagocytosis of MG, opens new avenues for prevention and therapeutic strategies against AD and provides solid experimental evidence and theoretical support.