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The hidden skeleton “gatekeeper” inside brain cells could help fight Alzheimer's

12 hours 11 minutes ago
Researchers have discovered that a microscopic skeleton inside neurons does much more than hold cells together. It acts as a gatekeeper that controls what brain cells absorb and when they absorb it. When this protective structure weakens, neurons rapidly take in harmful proteins associated with Alzheimer's disease, suggesting that stabilizing it could become a promising new strategy for preventing brain cell damage.

A small molecule reduces both parkinsonism and l-dopa-induced dyskinesia in animal models of Parkinson's disease

16 hours 49 minutes ago
Maximizing clinical benefits of therapeutics while minimizing adverse effects is a central challenge in drug development. For Parkinson's disease (PD), l-3,4-dihydroxyphenylalanine (l-dopa) is the most effective treatment available, but chronic use is associated with periods of reduced efficacy (motor fluctuations) and the debilitating on-target side effect of l-dopa-induced dyskinesia. To disentangle the molecular mechanisms underlying l-dopa's antiparkinsonian effects versus its dyskinetic...
Aarash Bordbar

Functional segregation in Parkinson's disease

16 hours 49 minutes ago
The basal ganglia are characterized by somatotopic representation and are organized in parallel, functionally segregated corticostriatal circuits, but the impact of Parkinson's disease (PD) on this architecture is unknown. We mapped task-evoked dopamine release using [^(11)C]raclopride positron emission tomography/magnetic resonance in 13 early PD and 15 healthy control (HC) subjects during the performance of motor, cognitive, and reward tasks. In PD, motor tasks elicited decreased relative...
Dongning Su

Liver- and Immune-Enriched Molecular Signatures Associated With Mortality in Older Adults

16 hours 49 minutes ago
Quantifying biological aging requires biomarkers that capture multisystem physiological decline beyond chronological age. We aimed to compare the prognostic performance of plasma proteomics, metabolomics, and conventional clinical risk factors for all-cause mortality, and to characterize molecular pathways associated with mortality risk and age-related physiological decline. Untargeted plasma proteomics and metabolomics were profiled in 848 community-dwelling adults from the I-Lan Longitudinal...
Yi-Long Huang

Regulation of neutrophil homeostasis by the TNFAIP8 family of polarity proteins

16 hours 49 minutes ago
The extremely short life span of neutrophils is critical for immune homeostasis and immune defense against pathogens, but the molecular mechanisms underlying this phenomenon are not fully understood. Here we report that TNFAIP8 (TNF-α-induced protein 8) family of polarity proteins regulates neutrophil homeostasis by propagating phosphoinositide signaling. Genetic deletion of two members of the TNFAIP8 family, i.e., TIPE0 and TIPE1, resulted in spontaneous neutrophilia and hepatitis. TNFAIP8...
Han Wang

Long-term safety and efficacy of intracortical microstimulation in humans

16 hours 49 minutes ago
Intracortical microstimulation (ICMS) of somatosensory cortex can restore a sense of touch to people with spinal cord injury. In this early feasibility clinical trial (NCT01894802), we evaluated the safety, efficacy, and longevity of ICMS because there is a paucity of such long-term studies in humans. This information is crucial to the development of clinical neuromodulation devices, particularly for restoring touch, hearing, and vision. ICMS was delivered to five participants with spinal cord...
Charles M Greenspon

A comparative evaluation of brain MRI modalities, modality-specific measures, brain regions, and cognitive tests for brain age prediction

16 hours 49 minutes ago
Brain age estimation using machine learning has gained significant attention as a promising approach to assess cognitive health and aging. By analyzing structural and functional MRI data, these models can predict an individual's brain age, providing insights into neurological conditions and potential interventions. The purpose of this study is to compare the performance of different MRI modalities in predicting brain age and to determine the relative importance of specific brain regions. In this...
Hami Mahdavinataj

Age-associated microglial heterogeneity includes emergence of mobile microglial states

16 hours 49 minutes ago
Microglia maintain neuronal homeostasis through dynamic surveillance strategies that depend on their functional state. In the healthy brain, highly ramified microglia monitor neuronal integrity via motile processes and transient soma contacts. Aging is associated with reduced process motility and diminished expression of homeostatic markers, raising the question of how microglial surveillance adapts to these changes. Here, we used ex vivo time-lapse imaging of acute cortical slices from young...
Sunitha Subhramanian