Jeffery W. Kelly

AA-20 promotes lipophagy by activating lysosomal acid lipase and CDK5, reducing lipid droplet accumulation and improving neurodegeneration-associated phenotypes in cellular and organoid models.

The paper provides a comprehensive survey of the ubiquitin-proteasome system (UPS) and estimates its size and scope within the human proteostasis network.

The paper identifies covalent ligands targeting a cryptic cysteine in CRBN, demonstrating their ability to inhibit neosubstrate degradation by trapping CRBN in an inactive conformation.

The paper introduces rank normalization to compare protein turnover across degradation pathways, revealing pathway-specific substrate preferences and proteaphagy.

The paper identifies tailocins as contaminants in ex vivo amyloid preparations and proposes strategies to detect and avoid them in cryo-EM.

This study identifies two mechanisms by which dipeptide esters disrupt lysosomal homeostasis: amyloid fibril formation and proximity labeling via Cathepsin C.

This study shows that sTREM2 inhibits bacterial amyloid CsgA formation and suppresses biofilm formation in uropathogenic E. coli.

This study identifies small molecules that stabilize diverse amyloidogenic immunoglobulin light chains by reducing conformational dynamics and proteolysis.

The paper characterizes extracellular vesicles from Alzheimer's disease and wild-type cerebrocortical organoids, finding differences in size, membrane structure, and proteomic content.

This study shows that APOE4 impairs lipoprotein secretion in microglia, leading to lysosomal and mitochondrial dysfunction and a proinflammatory phenotype.

This paper provides processing guidelines for helical reconstruction of amyloids using cryoSPARC, highlighting current capabilities and limitations while advocating for amyloid-specific parameter optimization.

This study uses proteomics and 3D imaging to show that ATTR cardiac amyloidosis involves microangiopathy, capillary occlusion, and vascular basement membrane congestion.

This study shows that beta-hydroxybutyrate (betaHB) improves neuronal Tau proteostasis and reduces Tau aggregation in tauopathy models, independent of its ketolysis for ATP production.

The paper develops a HaloTag-4R-Tau sensor to study tau clearance in iNeurons and identifies Neddylation inhibition as a method to promote tau degradation.

This study uses human iPSC-derived cortical organoids to model familial Alzheimer's disease and shows that autophagy activators reduce pathological Tau and Aβ accumulation and rescue synaptic loss.

This study identifies AA263 analogs that enhance ER proteostasis by targeting ER protein disulfide isomerases, correcting protein misfolding in disease models.

AA147 reduces oligodendrocyte loss and demyelination in a mouse model of MS by activating ATF6 and NRF2 pathways, improving clinical symptoms and microglia activation.

This study uses cryo-EM to reveal the conformational landscape of human transthyretin, uncovering asymmetries and new states relevant to ligand binding and amyloid formation.

This study shows that activating XBP1s reduces disease severity in CMT1B models by mitigating ER stress and mutant protein toxicity in Schwann cells.

The paper detects ATTR aggregates in plasma of polyneuropathic ATTR-V30M amyloidosis patients using a peptide probe and finds no correlation with age or gender.

The paper curates a list of 838 high-confidence components of the autophagy-lysosome pathway as part of a comprehensive effort to define the human proteostasis network.

The paper defines and annotates 959 genes comprising the human proteostasis network, focusing on translation, protein folding, and organelle-specific systems.

This study shows ATF6 is essential for human cone photoreceptor development and demonstrates that ATF6 activators can restore cone growth in patient-derived retinal organoids.

The paper identifies proteome-wide changes in mouse models of Alzheimer's disease, highlighting ApoE dysregulation and synaptic protein loss.