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Mutations in the phospholipase A2 group VI (PLA2G6) gene have been linked to autosomal recessive Parkinson's disease (PD), yet the molecular mechanisms remain poorly understood. This study provides the in vitro and in vivo evidence, specifically in dopaminergic neurons derived from patients with PD, that PLA2G6 loss-of-function disrupts the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM), a critical regulator of Ca^(2+) transfer and energy homeostasis. This study demonstrates...

Biomolecular condensates formed via liquid-liquid phase separation (LLPS) are essential for cellular organization. α-Synuclein, an amyloidogenic protein linked to Parkinson's Disease (PD), undergoes phase separation at high concentrations, but the influence of lipid membranes on this process remains unclear. Here, combining in vitro reconstitution, cell biology, and simulations, we show that membranous interfaces promote α-Synuclein condensation at physiologically relevant sub-critical...

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The rapidly developing search engines for glycopeptide identification and accumulated high-resolution glycoproteomic data underscore the need for robust downstream data mining platforms towards subsequently functional and mechanistic studies. Here, we introduce StrucGAP, a Structural Glycoproteomics Analysis Platform for scalable downstream data mining of site-specific N-glycoproteomics. It integrates modules for data quality control, overall glycan structural characterization, altered glycan...

We identified a new progeroid syndrome with severe neuropathy and intellectual deficits but its underlying cellular and molecular mechanism is unknown. Exome sequencing revealed a homozygous mutation in the IVNS1ABP gene, which encodes IVNS1ABP, an influenza virus non-structural protein-1 binding protein. To investigate disease mechanisms, we generated isogenic induced pluripotent stem cells (iPSCs) from patient fibroblasts and differentiated them into neural progenitor cells (NPCs). Mutant...

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The global challenge of population aging underscores the critical need to delay brain aging and cognitive decline, a pressing public health issue. The brain-gut-muscle axis is a complex regulatory network connecting skeletal muscle, gut microbiota, and the brain. It has received considerable research attention for its crucial role in maintaining brain health and counteracting aging. As a safe and effective non-pharmacological intervention, exercise modulates gut microbiota composition and...

INTRODUCTION: TAS2R38 is a taste receptor gene located on human chromosome 7 that influences sensitivity to bitter tastes and has been implicated in innate immunity, glucose level, and human longevity. However, its potential association with Alzheimer's Disease (AD) has not been explored. Identifying such a genetic connection could support developing new drugs or repurposing existing ones for AD treatment.

The gut microbiome influences brain function through the gut-brain axis via synthesis of neurotransmitters, production of metabolites affecting epithelial barrier integrity and immune modulation and signaling through the vagus nerve. In humans, microbiome diversity reflects healthy aging and predicts survival, while dysbiosis is increasingly implicated in neurodegenerative conditions including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and ALS. Fecal transplant studies in...

CONCLUSION: Age-related changes in balance control are task dependent. Older adults preserved static balance performance but demonstrated impaired reactive balance responses in dynamic tasks. Furthermore, static and dynamic balance rely on distinct control mechanisms, highlighting the need for separate assessments.

Fabricated platforms at an Australian wastewater lagoon soak up water pollution and methane

Transglutaminase 2 (TG2) is implicated in synucleinopathies including Parkinson's disease (PD) and dementia with Lewy bodies, as it promotes α-Synuclein (α-Syn) aggregation in vitro, and evidence for its activity is detected in Lewy bodies in human postmortem brains. Additionally, TG2 overexpression exacerbates α-Syn toxicity in double transgenic mice, while TG2 deletion mitigates the phenotype of α-Syn transgenic mice. Considering that TG2 is a multidomain and multifunctional protein, the...

Mitochondrial transplantation holds significant potential for the treatment of mitochondrial diseases. However, how to efficiently deliver exogenous mitochondria to somatic cells or tissues remains unresolved. We present a mitochondrial transplantation approach to deliver mitochondria into the cells and tissues of mice and monkeys with high efficiency, based on encapsulating mitochondria with vesicles derived from the plasma membrane of erythrocytes. Treatment with encapsulated mitochondria...

Neurofibrillary tangles, composed of excessively phosphorylated tau, are a core neuropathological hallmark of Alzheimer's disease (AD). However, therapeutic strategies aimed at directly clearing neurofibrillary tangles have demonstrated limited clinical efficacy, shifting the research focus towards the fundamental underlying mechanism- the dysregulation of tau phosphorylation. Evidence indicates that tau physiological phosphorylation is indispensable for microtubule stability and normal neuronal...

Aging is often associated with a maladaptive "stiffness" strategy of postural control, which limits adaptability and increases fall risk. Complex visuomotor training (e.g., juggling) may counteract this decline, but the relationship between biomechanical reorganization and cognitive cost reduction remains unclear. We hypothesized that juggling would induce a shift from stiffness to "active monitoring" and reduce the dual-task cost. This exploratory secondary analysis of a randomized crossover...

Natural light is severely affected by human impact on Earth, yet little is known about the roles light receptors have outside vision and rhythmic processes, despite their tremendously wide abundance. Here we show that loss-of-function of the light-receptive cryptochrome (l-cry) in marine bristleworms significantly increases lifespan and adult size, similarly to wild-types reared in constant darkness. Quantitative transcriptomics revealed hormonal players crucial for invertebrate and vertebrate...

Partial cellular reprogramming can modulate aging-associated decline across multiple tissues. However, whether targeting memory-encoding ensembles within specific brain regions is sufficient to restore cognitive function has remained unknown. In this issue of Neuron, Berdugo-Vega et al. show that engram rejuvenation rescues memory deficits and restores epigenetic-transcriptional features and intrinsic excitability.

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White matter (WM) is a key substrate for interregional neural communication and cognitive function but the role of WM glucose metabolism in cognitive aging has been understudied. Using multimodal neuroimaging (MRI, FDG-PET, amyloid-PET) from 3142 participants (15,287 visits) across two studies, we examined the contribution of WM to cognition and identified divergent WM signatures. Higher glucose metabolism in expected WM (EWM; corpus callosum and cingulum) was associated with better cognition,...