Ferroptosis requires not only the accumulation of iron ions, but also changes in many ferroptosis-related regulators, including a decrease in GPX4 and inhibition of SLC7A11 for classical ferroptosis, a deletion of FSP1 or GCH1. Surprisingly, adipose tissue (AT) in the obesity conditions is also accompanied by iron buildup, decreased GSH, and increased ROS. On the neurological side, the pro-inflammatory factor released by AT may have first caused ferroptosis in the vagus nerve by inhibiting of the NRF2-GPX4 pathway, resulting in disorders of the autonomic nervous system. On the immune side, obesity may cause M2 macrophages ferroptosis due to damage to iron-rich ATMs (MFe^hi) and antioxidant ATMs (Mox), and lead to Treg cells ferroptosis through reductions in NRF2, GPX4, and GCH1 levels. At the same time, the reduction in GPX4 may also trigger the ferroptosis of B1 cells. In addition, some studies have also found the role of GPX4 in neutrophil autophagy, which is also worth pondering whether there is a connection with ferroptosis. In conclusion, this review summarizes the associations between neuroimmune regulation associated with obesity and ferroptosis, and on the basis of this, highlights their potential molecular mechanisms, proposing that ferroptosis in one or more cells in a multicellular tissue changes the fate of that tissue.

Parkinson’s disease (PD), as a neurodegenerative disorder, is characterized primarily by damage to the central nervous system, accompanied by astrocyte dysfunction and the activation of ferroptosis. Recent studies have shown that oligodendrocytes also exhibit functional abnormalities in the brains of PD patients and are involved in the ferroptotic process. However, it remains unclear whether there is an interaction between oligodendrocytes and astrocytes and how they induce neuronal ferroptosis. Here, we employed single-nucleus sequencing and spatial transcriptomics to characterize the intercellular communication network between oligodendrocytes and astrocytes in the PD environment. Among these, astrocytes are the primary recipients of signals sent by oligodendrocytes in the FGF (Fibroblast growth factors) signaling pathway. In PD, the communication intensity is weakened, involving FGF1 and FGF9 and their receptors FGFR1, FGFR2, and FGFR3. Subsequently, we further validated the significant activation of mitochondrial oxidative phosphorylation processes within oligodendrocytes and astrocytes in PD mice, and that astrocytes might also involve the interaction of Mt1 and Ca²⁺. Additionally, we demonstrated a significant reduction in the number of DA neurons in the SN region and a notable activation of ferroptosis, alongside a significant decrease in the antioxidant pathway NRF2/SLC7A11/GPX4. In summary, our data elucidate that ferroptosis in the midbrain SN region preferentially occurs in astrocytes under the dysregulation of oligodendrocytes, leading to ferroptosis in DA neurons. Thus, our study highlights the crucial role of oligodendrocyte-astrocyte crosstalk in driving neuronal inactivation and inflammatory expansion in PD.

SOCS (Suppressor of Cytokine Signalling) proteins are intracellular negative regulators that primarily modulate and inhibit cytokine-mediated signal transduction, playing a crucial role in immune homeostasis and related inflammatory diseases. SOCS act as inhibitors by regulating the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, thereby intervening in the pathogenesis of inflammation and autoimmune diseases. Recent studies have also demonstrated their involvement in central immunity and neuroinflammation, showing a dual functionality. However, the specific mechanisms of SOCS in the central nervous system remain unclear. This review thoroughly elucidates the specific mechanisms linking the SOCS-JAK-STAT pathway with the inflammatory manifestations of neurodegenerative diseases. Based on this, it proposes the theory that SOCS proteins can regulate the JAK-STAT pathway and inhibit the occurrence of neuroinflammation. Additionally, this review explores in detail the current therapeutic landscape and potential of targeting SOCS in the brain via the JAK-STAT pathway for neuroinflammation, offering insights into potential targets for the treatment of neurodegenerative diseases.

Background: Mild Cognitive Impairment (MCI), a transition between normal aging and dementia, is linked to higher dementia risk and potential reversibility. Type 2 Diabetes Mellitus (T2DM), affecting over 537 million adults worldwide, increases susceptibility to MCI, with higher cognitive decline prevalence in diabetic populations. Previous meta-analyses focused on isolated factors, neglecting multidimensional interactions. This study synthesizes T2DM-MCI risk factors across clinical, lifestyle, and biochemical dimensions to support early identification and intervention of cognitive dysfunction in T2DM populations.Materials and Methods: This systematic review and meta-analysis, following PRISMA guidelines, searched five databases for articles published from January 1, 2014, to December 31, 2024. Studies were screened based on predefined criteria, with data extracted independently by two researchers. Quality was assessed using Newcastle-Ottawa Scale (NOS) and Joanna Briggs Institute (JBI) tools. Data were analyzed using RevMan software, with odds ratio (OR) and 95% CI as effect size measures. Heterogeneity was assessed using I² statistics, and subgroup analyses were conducted for factors with ≥10 studies.Results: 30 studies with 10,469 participants were included. Prevalence rate of MCI in T2DM was 44.1%. Significant associations were found between T2DM-MCI and age (OR = 1.06, P = 0.01), female sex (OR = 1.23, P = 0.05), diabetes duration (OR = 1.07, P = 0.03), education (OR = 0.82, P = 0.0001), smoking (OR = 1.44, P = 0.003), hypertension (OR = 2.25, P < 0.001), cardiovascular disease (CVD) (OR = 2.61, P < 0.001), glycated hemoglobin (HbA1c) (OR = 1.33, P = 0.001), and homeostasis model assessment of insulin resistance (HOMA-IR) (OR = 1.95, P = 0.02).Conclusion: This meta-analysis identifies advanced age (≥60 years), female sex, prolonged Diabetes duration (8–9 years), elevated HbA1c (>9%), and low education (≤6 years) as key predictors of MCI in T2DM, with significant dose-response relationships. Vascular comorbidities, insulin resistance, and inflammatory markers further exacerbate risks. Clinical priorities include rigorous glycemic control (HbA1c <7%), targeted cognitive screening for high-risk subgroups, and multidisciplinary care for patients with microvascular complications. However most of the studies included in this study come from Chinese people, so the generalization of the results may be limited.Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD420250637336.

Exercise has been widely recognized as an effective regimen in mitigating cognitive decline. However, the effect of multi-component exercise (i.e., combination of two or more types of exercise) on cognitive function and its subdomains in older adults remains unclear. This meta-analysis aimed to explore the effects of multi-component exercise on cognitive functions in elderly individuals with cognitive impairment and identify optimal prevention and treatment strategies. A systematic search was conducted on PubMed, EBSCOhost, Web of Science, and Embase to identify relevant randomized controlled trials assessing the effect of multi-component exercise on cognitive function in the elderly. Thirteen studies with 1,776 participants were included in the analysis using Revman 5.4 software. The results showed that multi-component exercise had a significant effect on mitigating cognitive function decline in the elderly, with a pooled effect size of SMD = 0.31 (95% CI: 0.08, 0.55; p = 0.009). The results of subgroup analysis showed that interventions with ≥3 days/week, 12–24 weeks duration, and ≤ 40 min/session were significantly superior to other frequencies, durations, and lengths, with all p-values <0.05. Additionally, multi-component exercise had the most pronounced effects on executive function, visual memory, and verbal memory in patients with mild cognitive impairment (MCI). In conclusion, multi-component exercise can delay the decline in cognitive function in the elderly, and the intervention effects are modulated by various variables. Optimal intervention effects were observed with an exercise frequency of three or more times per week, a duration of 12 to 24 weeks, and a time per session of 40 min or less, particularly for improving executive function, visual memory, and verbal memory in patients with MCI.

This study aimed to examine the prevalence of type 2 diabetes (T2D) and the independent and joint associations of sleep duration and different volumes of physical activity (PA) with T2D in the China Health and Retirement Longitudinal Study (CHARLS). The prevalence of T2D among the Chinese population aged 45 years and older was estimated for the years 2011, 2013, 2015, 2018, and 2020. Data from 2020 were used to examine the independent and joint associations of sleep duration and different volumes of PA with T2D. Sleep duration was classified into three categories: short (< 6 h/day), normal (6–8 h/day), and long (> 8 h/day). PA volumes were classified based on the IPAQ recommendations as follows: light-volume PA (LPA, < 600 MET-minutes/week), moderate-volume PA (MPA, 600–3000 MET-minutes/week), and vigorous-volume PA (VPA, > 3000 MET-minutes/week). The data were statistically analyzed using a t-test and analysis of variance (ANOVA). Multivariate logistic regression models were used to examine the independent and joint associations of PA and sleep duration with T2D. The prevalence of T2D in the LPA and short sleep groups increased from 13.35% (95% CI = 10.41–16.75) and 11.52% (95% CI = 10.01–13.15) in 2011 to 17.27% (95% CI = 15.09–19.62) and 16.28% (95% CI = 15.34–17.25) in 2020, respectively. Compared with LPA, VPA was associated with lower odds of T2D (Model 3, OR = 0.82, 95% CI = 0.69–0.97). Compared to individuals with normal sleep duration, those with short sleep duration had a higher likelihood of T2D (Model 3, OR = 1.10, 95% CI = 1.08–1.22), whereas long sleep duration did not show a significant association (Model 3, OR = 1.03, 95% CI = 0.86–1.23). The risk of developing T2D was approximately 35% lower for individuals with LPA and normal sleep duration compared to those with LPA and short sleep duration (Model 3, OR = 0.65, 95% CI = 0.46–0.91). In the VPA group, the mitigation effect of exercise on T2D was observed regardless of sleep duration (Model 3, short: OR = 0.73, 95% CI = 0.56–0.95; normal: OR = 0.65, 95% CI = 0.51–0.85; long: OR = 0.63, 95% CI = 0.45–0.89). The prevalence of T2D among middle-aged and older adults in China increased substantially from 2011 to 2020. Short sleep duration is associated with higher odds of developing T2D. However, engaging in VPA mitigates this risk, even in those with insufficient sleep.