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Study of mitochondria suggests new treatment strategy for Alzheimer’s and other diseases

A long-term brain study found that common risks such as smoking, high blood pressure, heart disease, and high blood lipids were strongly linked to damage associated with vascular dementia. The findings suggest that healthier lifestyle choices could help delay dementia by reducing several harmful brain changes at once.

Mutations in lysosomal enzyme glucocerebrosidase (GBA), the most common genetic risk factor for Parkinson disease (PD), exacerbate α-synuclein pathology through unclear mechanisms. Here, we report, in a large cohort, that GBA-mutated PD patients exhibit lower serum cholesterol levels. By introducing the most common GBA variant in our cohort, L444P, into human α-synuclein knock-in mice, we noted that the mice exhibited behavioral and molecular pathological PD features at 12 months of age....

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a key role in responding to viral genomes and endogenous DNA byproducts by inducing inflammatory pathways. Its roles in senescence and in the response to telomere shortening have also recently been proposed. To address its role in age-related pathologies and decreased longevity associated with short telomeres, we generated double-mutant mice deficient for STING and either the telomerase RNA component (TERC)...

CONCLUSIONS: A fully automated IVR system is a valid and feasible tool for frailty screening in community-dwelling older adults. Requiring no internet or human intervention, it offers a scalable solution for population-level frailty surveillance, especially in resource-limited settings.

Mitochondrial dysfunction and abnormal energy metabolism are important pathological features of Alzheimer's disease (AD). This study investigates how mitochondrial protease YME1L1 affects mitochondrial function and its upstream regulation in the pathogenesis of AD. The AD model was established by using APP/PS1 transgenic mice, primary neurons treated with Aβ1-42, and HT22 cells. The silencing of YME1L1 was achieved to evaluate its effects on mitochondrial function and OPA1 protein hydrolysis....

Parkinson's disease (PD) is a multisystemic disorder that manifests through motor and non-motor symptoms. Motor dysfunction results from the degeneration of dopamine-producing neurons in the substantia nigra pars compacta. Increasing evidence suggests that synapse dysfunction precedes neuronal loss by years. Still, early synaptic alterations in PD remain poorly understood. Here, we integrate literature meta-analysis and multi-omics with biochemical, imaging, and electrophysiological measurements...

SQSTM1/p62 (sequestosome 1) is an important receptor protein involved in many cellular signaling processes, including macroautophagy/autophagy. It is a molecular hub for cellular homeostasis and cellular responses. Within autophagy, SQSTM1 targets ubiquitinated cargo for degradation, maintaining cellular proteostasis. Structurally, SQSTM1 consists of several domains that facilitate its binding to ubiquitinated cargo, the formation of SQSTM1 aggregate inclusions, interactions with MAP1LC3/LC3,...

Scalable clinical markers of neurocognitive vulnerability in aging are needed, particularly in settings where biomarker access remains limited. Instrumental activities of daily living (IADLs) capture cognitively demanding everyday behavior and may provide a low-cost, repeatable functional marker of elevated risk. We harmonized longitudinal data from four population-based aging cohorts-CHARLS, ELSA, HRS, and SHARE-including adults aged ≥50 years with eligible baseline assessments. IADL impairment...

Alzheimer's disease (AD) is a chronic, progressive neurodegenerative condition that is characterized by an increasing incidence rate due to global population aging, resulting in a significant social and economic burden. Current pharmacological interventions offer only limited relief and are unable to halt neuronal loss and cognitive decline. Therefore, safe and effective non-pharmacological interventions (NPIs) are needed for the management of AD. This review systematically synthesizes...

High-fidelity single-nucleotide-resolution mapping of abasic (AP) sites in mammalian genomes remains technically challenging due to low abundance and high background. Here we present DEPACE-seq (Dual-End PAB-Conjugated Endo IV-Cleaved Sequencing), a robust and easy-to-implement method for precise genome-wide profiling of AP sites. DEPACE-seq employs an N-pyrrolyl-alanine-2,2'-(ethylenedioxy)bis(ethylamine)-biotin (PAB) probe that selectively conjugates AP sites via a mild Pictet-Spengler...

Genetic changes may set off a chain reaction that causes the spine’s natural shock absorbers to harden and deteriorate. Zebrafish with a faulty collagen-related gene developed mineral buildup and spinal fusion similar to human disc disease. Researchers were able to reduce the damage using an existing osteoporosis drug and by targeting fat metabolism. The discovery points to several exciting possibilities for future back pain treatments.