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Tau hyperphosphorylation impairs cooperative binding to microtubules and perturbs organelle trafficking in neurons

1 week 6 days ago
Tau, a neuronal microtubule-associated protein (MAP), organizes the axonal cytoskeleton, and regulates intracellular transport. Tau hyperphosphorylation is linked to neurodegeneration in tauopathies, including Alzheimer's disease. Tau binds microtubules cooperatively to form cohesive envelopes, which are thought to control access to the microtubule lattice and regulate the activity of motor proteins and other MAPs. However, how disease-related perturbations affect tau dynamics and its function...
Daniel Beaudet

BAG3 coordinates astrocytic proteostasis of Alzheimer's disease-linked proteins via proteasome, autophagy, and retromer interactions

1 week 6 days ago
Bcl-2-associated athanogene 3 (BAG3) is a mediator of chaperone-assisted selective autophagy, and in the brain, is most highly expressed in astrocytes. However, its role in astrocytes remains poorly defined. Given the genetic and pathological links of BAG3 to proteostasis and neurodegenerative diseases, we investigated how BAG3 contributes to astrocyte function and Alzheimer's disease (AD). To define its function and relevance, we used single-nucleus RNA sequencing to confirm BAG3 enrichment in...
Zachary M Augur

Hypomorphic STING1/TMEM173 variants may support immuno-metabolic resilience in aging people living with HIV

1 week 6 days ago
Antiretroviral therapy (ART) has significantly increased life expectancy of people living with HIV (PLWH). Nonetheless, despite effective virological control, PLWH are faced with accelerated aging, characterized by higher prevalence of age-related comorbidities than the general population. Persistent inflammation and activation of innate immunity seem to drive this immunosenescent phenotype. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is increasingly...
Isabella Zanella

Masking phosphatidylserine prevents neuronal loss in two distinct <em>Drosophila</em> models of neurodegeneration

1 week 6 days ago
Neuronal loss is a hallmark of neurodegenerative diseases. Phosphatidylserine (PS), a key "eat me" signal, is exposed on stressed viable neurons, triggering their premature phagocytosis by activated glia. We investigated whether PS masking could serve as a universal strategy to prevent neuronal loss in two distinct Drosophila models of neurodegeneration: an adult-stage-specific knockdown of skpA and a Huntington's disease model initiated during embryogenesis. Both models exhibit neuronal loss,...
Naden Khateb

Deep Learning Predicts Hematopoietic Stem Cell Aging From 3D Chromatin Images

1 week 6 days ago
The functional decline of the hematopoietic system during aging affects organismal function and contributes to reduced healthspan. Quantifying hematopoietic aging holds great scientific and clinical relevance. Alterations in chromatin architecture are a well-established hallmark of aging that encode rich and informative signatures of the aging process, yet they remain largely unexplored as quantitative markers. Here, we present an interpretable deep learning approach based on convolutional...
Pablo Iáñez Picazo

Autophagy Flux Is Remodeled Sex- and Cell Type-Specifically During Human Aging, and Is Linked to Reduced Physical Function in Older Adults

1 week 6 days ago
Autophagy is widely proposed to decline with age; however, direct evidence across human cell types remains limited. Moreover, it is unclear whether age-associated changes in autophagy-gene transcription are accompanied by corresponding changes in autophagic activity, and whether autophagic activity relates to physiological function during aging. We performed transcriptomic and functional autophagy analyses across subject-matched human cell types from a healthy aging cohort. Autophagy-related...
Tatiana M Moreno

Resetting the body clock could help the brain recover after stroke

1 week 6 days ago
Strengthening the body’s natural daily rhythms helped mice recover after stroke by improving the brain’s waste-clearing system and reducing lingering inflammation. The approach worked even when treatment began three days after the stroke, suggesting circadian-based therapies could eventually offer a new way to support long-term recovery.

Scientists found a surprising driver of Alzheimer’s outside the brain

1 week 6 days ago
Scientists found that immune cells contributing to Alzheimer’s-related brain damage may be activated in lymph nodes outside the brain before traveling into the nervous system. Blocking this pathway in mice dramatically reduced neurodegeneration and preserved cognitive abilities, pointing to a potentially more accessible treatment target.