Parkinson's disease (PD) is one of the most common neurodegenerative diseases with complex etiology in sporadic cases. Accumulating evidence suggests that oxidative stress and defects in mitochondrial dynamics are associated with the pathogenesis of PD. The oxidative stress and mitochondrial dynamics are regulated strictly by peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). We investigated whether acetylation and phosphorylation of PGC-1α contribute to protecting neuronal cell against oxidative stress.

Female fertility decreases with age. A decline in oocyte quality plays a key role in reproductive problems in older women. Whether advanced maternal age (AMA) is associated with a decline in endometrial receptivity (ER) remains controversial. A systematic review and meta-analysis were conducted to evaluate the relationship between AMA and ER. Eighteen eligible studies were included in this meta-analysis. Of the 18 studies, 17, 8, 14, and 9 studies reported the impact of AMA on clinical pregnancy rate (CPR), implantation rate (IR), miscarriage rate (MR), and live birth rate (LBR), respectively. The combined results showed a trend (without significance) toward lower CPR in women with AMA than in younger women. A similar trend of worse outcomes in terms of IR was observed in women with AMA. A significantly higher MR and lower LBR were observed in infertile women with AMA than in younger women. In conclusion, there was a slightly lower IR and CPR without significance; however, significantly increased MR and decreased LBR were observed in women with AMA than in younger women, indicating that AMA is related to the decline of ER. Further prospective cohort studies with a preimplantation genetic testing for aneuploidy model are needed to observe the relationship between AMA and ER and explore the possible mechanisms.

Evidence on the individual and combined relationship of physical activity (PA) and fish oil supplement use on the incidence of Parkinson's disease (PD) risk remains lacking.

The mechanisms of neuronal damage in hypoxic cerebral cortex are complicated. Recent studies indicated that deregulation of Cdk5 was involved in neuronal death induced by hypoxia (1% O2). However, the pathological effect of Cdk5 is not fully elucidated. Therefore, in order to decipher the effect of Cdk5 on cellular death in hypoxic condition, the Cdk5 and its activator p35/p25 were investigated in cortical neurons at 10 DIV (Days In Vitro). Upon exposure to hypoxia, the cortical neurons showed a time-dependent increase of neuronal death compared to normoxia-treated control neurons. In correlation to the increase of neuronal death under hypoxia, the level of p25, a truncated form of p35, also increased in a time-dependent manner. Importantly, inhibition of Cdk5 kinase activity by roscovitine protected neurons from death under hypoxic stress. In contrast, ectopic upregulation of Cdk5 kinase activity in neurons expressing p25 led to an increase of neuronal death in comparison to control neurons expressing GFP. It suggests that ectopic increase of Cdk5 kinase activity through conversion of p35 to p25 is involved in the process of neuronal death induced by hypoxia.

Mitochondrial dysfunction and oxidative stress are closely associated with the pathogenesis of Parkinson's disease. Peroxisome proliferator-activated receptor γ coactivator 1 alpha (PGC-1α) is thought to play multiple roles in the regulation of mitochondrial biogenesis and cellular energy metabolism. We recently reported that altering PGC-1α gene expression modulates mitochondrial functions in N-methyl-4-phenylpyridinium ion (MPP+) treated human SH-SY5Y neuroblastoma cells, possibly via the regulation of Estrogen-related receptor α (ERRα), nuclear respiratory factor 1 (NRF-1), nuclear respiratory factor 2 (NRF-2) and peroxisome proliferator-activated receptor γ (PPARγ) expression. In the present study, we aimed to further investigate the potential beneficial effects of PGC-1α in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated C57BL mice.

Increasing evidence suggests an association between pro-inflammatory diets and cognitive function. However, only a few studies based on small sample sizes have explored the association between pro-inflammatory diets and dementia using the dietary inflammatory index (DII). Additionally, the relationship between DII and different subtypes of dementia, such as Alzheimer's dementia and vascular dementia, remains largely unexplored. Given the changes in brain structure already observed in patients with dementia, we also investigated the association between DII and magnetic resonance imaging (MRI) measures of brain structure to provide some hints to elucidate the potential mechanisms between pro-inflammatory diet and cognitive decline.

Hearing aid usage has been linked to improvements in cognition, communication, and socialization, but the extent to which it can affect the incidence and progression of dementia is unknown. Such research is vital given the high prevalence of dementia and hearing impairment in older adults, and the fact that both conditions often coexist. In this study, we examined for the first time the effect of the use of hearing aids on the conversion from mild cognitive impairment (MCI) to dementia and progression of dementia.

The effective management and therapies for Parkinson's disease (PD) require appropriate clinical evaluation. The Parkinson's KinetiGraph (PKG) is a wearable sensor system that can monitor the motion characteristics of PD objectively and continuously. This study was aimed to assess the correlations between PKG data and clinical scores of bradykinesia, rigidity, tremor, and fluctuation. It also aims to explore the application value of identifying early motor symptoms. An observational study of 100 PD patients wearing the PKG for ≥ 6 days was performed. It provides a series of data, such as the bradykinesia score (BKS), percent time tremor (PTT), dyskinesia score (DKS), and fluctuation and dyskinesia score (FDS). PKG data and UPDRS scores were analyzed, including UPDRS III total scores, UPDRS III-bradykinesia scores (UPDRS III-B: items 23-26, 31), UPDRS III-rigidity scores (UPDRS III-R: item 22), and scores from the Wearing-off Questionnaire (WOQ-9). This study shows that there was significant correlation between BKS and UPDRS III scores, including UPDRS III total scores, UPDRS III-B, and UPDRS III-R scores (r = 0.479-0.588, p ≤ 0.001), especially in the early-stage group (r = 0.682, p < 0.001). Furthermore, we found that BKS in patients with left-sided onset (33.57 ± 5.14, n = 37) is more serious than in patients with right-sided onset (29.87 ± 6.86, n = 26). Our findings support the feasibility of using the PKG to detect abnormal movements, especially bradykinesia in PD. It is suitable for the early detection, remote monitoring, and timely treatment of PD symptoms.

New therapies are urgently needed for Alzheimer's disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China.

Population-based studies reveal that apolipoprotein E (APOE) ε4 gene allele is closely associated with late-life depression (LLD). However, its exact role and underlying mechanism remain obscure. The current study found that aged apoE4-targeted replacement (TR) mice displayed obvious depression-like behavior when compared with age-matched apoE3-TR mice. Furthermore, apoE4 increased stress-induced depression-like behaviors, accompanied by declines in the hippocampal 5-HT (1A) radioligand [18F] MPPF uptake evidenced by positron emission tomography (PET). In [18F]-fluorodeoxyglucose PET ([18F]-FDG PET) analyses, the FDG uptake in the prefrontal cortex, temporal cortex and hippocampus of apoE4-TR mice significantly declined when compared with that of apoE3-TR mice after acute stress. Further biochemical analysis revealed that ATP levels in the prefrontal cortex of apoE4-TR mice decreased during aging or stress process and ATP supplementation effectively rescued the depression-like behaviors of elderly apoE4-TR mice. In primary cultured astrocytes from the cortex of apoE-TR mice, apoE4, when compared with apoE3, obviously decreased the mitochondrial membrane potential, mitochondrial respiration, and glycolysis in a culture time-dependent manner. Our findings highlight that apoE4 is a potential risk factor of depression in elderly population by impairing the glucose metabolism, reducing ATP level, and damaging mitochondrial functions in astrocytes, which indicates that in clinical settings ATP supplementation may be effective for elderly depression patients with apoE4 carrier.

Parkinson's disease (PD), as a common neurodegenerative disease, currently has no effective therapeutic approaches to delay or stop its progression. There is an urgent need to further define its pathogenesis and develop new therapeutic targets. An increasing number of studies have shown that members of the sirtuin (SIRT) family are differentially involved in neurodegenerative diseases, indicating their potential to serve as targets in therapeutic strategies. Mitochondrial SIRT4 possesses multiple enzymatic activities, such as deacetylase, ADP ribosyltransferase, lipoamidase, and deacylase activities, and exhibits different enzymatic activities and target substrates in different tissues and cells; thus, mitochondrial SIRT4 plays an integral role in regulating metabolism. However, the role and mechanism of SIRT4 in PD are not fully understood. This study aimed to investigate the potential mechanism and possible regulatory targets of SIRT4 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice.

Trigeminal neuralgia (TN) is a neuropathic pain that occurs in branches of the trigeminal nerve. MicroRNAs (miRNAs) have been considered key mediators of neuropathic pain. This study was aimed to elucidate the pathophysiological function and mechanisms of miR-223-3p in mouse models of TN.