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A monoclonal antibody targeting the C-terminal of alpha-synuclein fibrils mitigates pathology in a Parkinson's disease model

17 hours 51 minutes ago
Parkinson's disease (PD) pathogenesis is driven by α-synuclein (α-syn) amyloid aggregation, with the flexible C-terminal region mediating pathological interactions with cellular receptors and facilitating disease propagation and neuroinflammation. Through immunization with human α-syn fibrils and iterative neuronal binding and propagation assays, we identify H21 as a high-affinity fibril-specific monoclonal antibody. H21 selectively binds to α-syn fibrils and specifically targets the C-terminal...
Shuyi Zeng

Cortical O<sub>2</sub> supply and metabolism are suppressed in the aged mice

17 hours 51 minutes ago
Current evidence suggests that the rejuvenating effects of parabiosis on brain function arise from the exchange of blood factors that enhance synaptic plasticity, promote neurogenesis, and reduce neuroinflammation in aged animals. However, aging is also associated with diminished tissue oxygenation. Here, we report that erythrocytes (red blood cells, RBCs) from aged mice exhibit reduced responsiveness to low oxygen tension (PO(2)) and release O(2) slower than those from young mice. In vivo,...
Hongyi Kang

MTFR1L is a cardiac antiaging factor for maintenance of mitochondrial homeostasis

17 hours 51 minutes ago
Mitochondrial dysfunction is a hallmark of aging and a key contributor to age-related diseases including cardiovascular disease. However, molecular pathways that safeguard mitochondrial homeostasis in the aging heart remain poorly understood. Here, we identify MTFR1L as a regulator of mitophagy that binds p-S65-Ub, a key signal amplifying the PINK1/Parkin axis. We find that MTFR1L is enriched in metabolically active tissues, particularly in the heart, where it regulates Parkin signaling. Genetic...
Le Shi

Age-driven dysbiosis: gut microbiota in the pathogenesis and treatment of aging disorders

17 hours 51 minutes ago
Aging, a complex physiological and molecular process, has undergone significant changes, of which gut microbiome composition has surfaced as an important key in the maintenance of neurological health. Recent studies have revealed the significant impact of age-related gut dysbiosis in the induction of neuroinflammation, metabolic syndrome, disruptions in gut-brain axis, and age-related neurological decline. Although significant studies have revealed the impact of the microbiome-gut-brain axis in...
Spandana Rajendra Kopalli

Hierarchical disruption of lateral prefrontal cortex gradients in cognitive aging

17 hours 51 minutes ago
The lateral prefrontal cortex (LPFC) plays a pivotal role in executive functions and exhibits a hierarchical rostro-caudal organization critical for higher-order cognition. Using connectome gradient mapping of resting-state fMRI data across young, middle-aged, and older adults (N = 478), we found preserved global gradient structure but significant compression of the principal gradient in older adults relative to middle-aged adults, particularly in dorsolateral (DLPFC) and frontopolar (FPC)...
Hai-Yan Hou

A multi-view DTI feature fusion framework for enhanced diagnosis of Alzheimer's disease

1 day 17 hours ago
Alzheimer's disease (AD) is an irreversible neurodegenerative disorder. Diffusion tensor imaging (DTI) is widely used to detect brain alterations for diagnosis, but most methods rely on single-scale information. Therefore, this study proposes the multi-view feature learning framework incorporating residual block-based 3D convolutional neural network (3D-CNN) for AD diagnosis. First, tract-based spatial statistics were applied to extract voxel-based features from fractional anisotropy (FA) and...
Jianping Qiao