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MEK1/2 inhibitors suppress pathological alpha-synuclein and neurotoxicity in cell models and a humanized mouse model of Parkinson's disease
The abnormal accumulation of misfolded proteins is a common hallmark of many neurodegenerative disorders. Among these proteins, α-synuclein (αsyn) is a well-characterized pathogenic protein in Parkinson's disease (PD) and other synucleinopathies. αsyn can be hyperphosphorylated and form pathological aggregates, leading to neurodegeneration. Thus, chemical modulators of pathological αsyn may suppress its downstream toxicity and provide entry points to therapeutic intervention. Here, we identified...
Crustal to mantle melt storage during the evolution of Hawaiian volcanoes
As the Pacific Plate migrates over the mantle plume below Hawai'i, magma flux decreases, resulting in changes in eruptive volume, style, and composition. It is thought that melt storage becomes deeper and ephemeral with the transition from highly voluminous tholeiitic (shield stage) to the less voluminous alkaline (post-shield and rejuvenation stages) magmatism. To quantitatively test this, we applied high-precision fluid inclusion barometry via Raman spectroscopy to samples from representative...
Loss of Subsidized Drug Coverage and Mortality among Medicare Beneficiaries
CONCLUSIONS: Loss of drug subsidies after Medicaid disenrollment was associated with higher mortality among low-income Medicare beneficiaries. (Funded by the National Institute on Aging and others.).
Correction to 'Broad repression of DNA repair genes in senescent cells identified by integration of transcriptomic data'
No abstract
Thymic Bmi-1 hampers gammadeltaT17 generation and its derived RORgammat-IL-17A signaling to delay cardiac aging
New immunosenescence targets for preventing senescence-associated pathological cardiac hypertrophy (SA-PCH) need to be explored. In the present study, with physiologically aged human and mouse samples, the IL-17A level increased with physiological aging, heart failure (HF), and SA-PCH and was negatively correlated with thymic Bmi-1 expression. Bmi-1^(f/f)LckCre^(+) mice and Bmi-1^(f/f) littermates were generated to determine whether Bmi-1 delayed T cell aging by maintaining thymic T cell...
Human and Mouse Alzheimer's Seeds Differentially Affect Amyloid Deposition and Microglia-Dependent Plaque Response in Aged Mice
Alzheimer's disease (AD) is a complex neurodegenerative proteinopathy in which Aβ and tau misfold and aggregate into entities that structurally unsettle native proteins, mimicking a prion-like or "seeding" process. These Aβ and tau "seeds" can arrange in different conformations or strains that might display distinct pathogenic properties. Furthermore, recent evidence suggests that microglia play a key role in the amyloidogenic event and can modulate the propagation and aggregation processes....