ShorterLab
@ShorterLab
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Countering deleterious phase transitions in ALS/FTD, PD, AD, and related disorders @Penn @PennMedicine @bb_upenn @BMBGGUPENN @PGGUPenn @PennNGG @CAMBUpenn
University of Pennsylvania
Joined January 2012
RNA G-Quadruplexes Function as a Tunable Switch of FUS Phase Separation:
biorxiv.org
FUS undergoes liquid-liquid phase separation (LLPS) to support essential cellular functions, but aberrant phase transitions promote toxic aggregation in neurodegenerative disease. Short RNA oligonu...
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Tubulin regulates stability and localization of STMN2 by binding preferentially to its soluble form:
rupress.org
Deng et al. employ two human cell models to elucidate how tubulin binding, membrane association, and protein stability converge in the biology of STMN2, a
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The neuron–astrocyte metabolic unit as a cornerstone of brain energy metabolism in health and disease:
nature.com
Nature Metabolism - Bolaños and Magistretti illustrate how intercellular metabolic cooperation underpins brain function and provide examples of how disruption of the neuron–astrocyte...
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Alzheimer’s decline slows with just a few thousand steps a day
nature.com
Nature - A modest increase in physical activity can delay cognitive decline by three years — or more.
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Physical activity as a modifiable risk factor in preclinical Alzheimer’s disease:
nature.com
Nature Medicine - In cognitively normal older adults at risk for Alzheimer’s dementia, physical inactivity was associated with faster tau protein buildup and cognitive decline.
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Mutant p53 protein accumulation is selectively targetable by proximity-inducing drugs:
nature.com
Nature Chemical Biology - Exploiting the high abundance of mutant p53 protein, a small molecule was developed that specifically binds to p53-Y220C mutants and delivers a mitosis blocker, killing...
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When TDP-43 Ghosts the Nucleus, Cryptic Poly-A Sites Rise from the Dead:
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A distal promoter and aberrant splicing enable canonical translation of out-of-frame proteins in Huntington’s disease
biorxiv.org
Expanded CAG trinucleotide repeats cause more than a dozen neurodegenerative diseases, including Huntington’s disease (HD). In several disorders, these repeats are translated in multiple reading...
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The potential of TDP-43 PET ligands for a biological diagnosis of TDP-43 proteinopathies:
nature.com
Nature Communications - Candidate PET ligands targeting pathological TDP-43 aggregates are characterized by Vokali and colleagues in a series of human tissue, cell/animal model, and non-human...
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Determining Multivalent Interactomes of Intrinsically Disordered Proteins in Phase-Separated Condensates in Live Cells
biorxiv.org
Many intrinsically disordered protein regions (IDRs) can form liquid-liquid phase separation (LLPS) condensates or related biomolecular assemblies via multivalent interactions, but how these intera...
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Integrative multiomic analysis links TDP-43-driven splicing defects to cascading proteomic disruption of ALS/FTD pathways:
biorxiv.org
Loss of nuclear TDP-43 is a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although TDP-43 is known to regulate RNA processing, including repression of cryptic...
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