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.

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.

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.

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.

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.