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The ER protein CANX (calnexin)-mediated autophagy protects against alzheimer disease

3 months 3 weeks ago
Although the relationship between macroautophagy/autophagy and Alzheimer disease (AD) is widely studied, the underlying mechanisms are poorly understood, especially the regulatory role of the initiation signaling of autophagy on AD. Here, we find that the ER transmembrane protein CANX (calnexin) is a novel interaction partner of the autophagy-inducing kinase ULK1 and is required for ULK1 recruitment to the ER under basal or starved conditions. Loss of CANX results in the inactivity of ULK1...
Hongtao Shen

The immunology of stroke and dementia

3 months 3 weeks ago
Ischemic stroke and vascular cognitive impairment, caused by a sudden arterial occlusion or more subtle but protracted vascular insufficiency, respectively, are leading causes of morbidity and mortality worldwide with limited therapeutic options. Innate and adaptive immunity have long been implicated in neurovascular injury, but recent advances in methodology and new experimental approaches have shed new light on their contributions. A previously unappreciated dynamic interplay of...
Costantino Iadecola

ApoE3 R136S binds to Tau and blocks its propagation, suppressing neurodegeneration in mice with Alzheimer's disease

3 months 3 weeks ago
PSEN1 E280A carrier for the APOE3 Christchurch variant (R136S) is protected against Alzheimer's disease (AD) symptoms with a distinct anatomical pattern of Tau pathology. However, the molecular mechanism accounting for this protective effect remains incompletely understood. Here, we show that the ApoE3 R136S mutant strongly binds to Tau and reduces its uptake into neurons and microglia compared with ApoE3 wild type (WT), diminishing Tau fragmentation by asparagine endopeptidase (AEP),...
Guiqin Chen

CRISPRi-based screens in iAssembloids to elucidate neuron-glia interactions

3 months 3 weeks ago
The complexity of the human brain makes it challenging to understand the molecular mechanisms underlying brain function. Genome-wide association studies have uncovered variants associated with neurological phenotypes. Single-cell transcriptomics have provided descriptions of changes brain cells undergo during disease. However, these approaches do not establish molecular mechanism. To facilitate the scalable interrogation of causal molecular mechanisms in brain cell types, we developed a 3D...
Emmy Li

Brain mechanical properties predict longitudinal cognitive change in aging and Alzheimer's disease

3 months 3 weeks ago
Age-related cognitive decline is a complex phenomenon that is influenced by various neurobiological processes at the molecular, cellular, and tissue levels. The extent of this decline varies between individuals and the underlying determinants of these differences are not fully understood. Two of the most prominent signs of cognitive decline in aging are the deterioration of episodic memory, which is a hallmark of Alzheimer's disease (AD), and the nearly always accompanying atrophy of the medial...
KowsalyaDevi Pavuluri

Deep learning reveals diverging effects of altitude on aging

3 months 3 weeks ago
Aging is influenced by a complex interplay of multifarious factors, including an individual's genetics, environment, and lifestyle. Notably, high altitude may impact aging and age-related diseases through exposures such as hypoxia and ultraviolet (UV) radiation. To investigate this, we mined risk exposure data (summary exposure value), disease burden data (disability-adjusted life years (DALYs)), and death rates and life expectancy from the Global Health Data Exchange (GHDx) and National Data...
Amanuel Abraha Teklu

Lung endothelial cell senescence impairs barrier function and promotes neutrophil adhesion and migration

3 months 3 weeks ago
Cellular senescence contributes to inflammation and organ dysfunction during aging. While this process is generally characterized by irreversible cell cycle arrest, its morphological features and functional impacts vary in different cells from various organs. In this study, we examined the expression of multiple senescent markers in the lungs of young and aged humans and mice, as well as in mouse lung endothelial cells cultured with a senescence inducer, suberoylanilide hydroxamic acid (SAHA),...
Maliheh Najari Beidokhti

Inhaled xenon modulates microglia and ameliorates disease in mouse models of amyloidosis and tauopathy

3 months 3 weeks ago
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. Antiamyloid antibody treatments modestly slow disease progression in mild dementia due to AD. Emerging evidence shows that homeostatic dysregulation of the brain immune system, especially that orchestrated by microglia, plays an important role in disease onset and progression. Thus, a major question is how to modulate the phenotype and function of microglia to treat AD. Xenon (Xe) gas is a noble gas used in human patients...
Wesley Brandao

A nanoparticle-based wireless deep brain stimulation system that reverses Parkinson's disease

3 months 3 weeks ago
Deep brain stimulation technology enables the neural modulation with precise spatial control but requires permanent implantation of conduits. Here, we describe a photothermal wireless deep brain stimulation nanosystem capable of eliminating α-synuclein aggregates and restoring degenerated dopamine neurons in the substantia nigra to treat Parkinson's disease. This nanosystem (ATB NPs) consists of gold nanoshell, an antibody against the heat-sensitive transient receptor potential vanilloid family...
Junguang Wu