#PharmSKy

Alzheimer’s Aβ catalyzes Tau phase separation and aggregation via early nanocluster solubilization | Nature Communications Extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated Tau are the two main pathological hallmarks of Alzheimer’s disease (AD). Although the co-occurrence and synergistic effects of Aβ and Tau are well established, the mechanisms underlying their interplay in a biomolecular condensate environment remain unclear. Here we show that Aβ40 does not undergo liquid–liquid phase separation (LLPS) but significantly enhances Tau phase separation and is recruited into Tau condensates. This recruitment alters condensate physicochemical properties, accelerates liquid-to-solid maturation, promotes Tau amyloid fibril formation, and increases Tau-mediated cytotoxicity. Notably, prior to condensate formation, Aβ40 transiently solubilizes Tau nanoclusters into smaller species. Simulations further indicate that early interactions are non-specific and mediated by Tau repeat domains, ultimately promoting pathogenic aggregation. These finding

Alzheimer's Aβ40 enhances Tau phase separation and aggregation by solubilizing early nanoclusters, revealing key interplay in disease pathology. PMID:41807382, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-70083-1 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

A person stands smiling in a library archive, surrounded by shelves filled with books and boxes. They rest a hand on an open filing cabinet drawer containing organized folders. The background is full of colorful sticky notes.

Professor Lucas Richert has received an Honorary Membership from the American #Pharmacists Association for his work bridging #pharmacy's past with its present and future.

Learn how he's been documenting, contextualizing, and elevating the evolving role of pharmacy. #PharmSky https://bit.ly/3NT5vm0

Excited to share that our latest review marine compounds for various medical uses has been published in Marine Drugs 🧪💊 #science #pharmsky www.mdpi.com/1660-3397/24...

https://doi.org/10.1126/science.ads1246 No description available

Etv3 in dendritic cells is key for maintaining immune balance; its absence causes Treg cell expansion and T cell activation issues. 🧬 PMID:41678619, Science 2026, @ScienceMagazine https://doi.org/10.1126/science.ads1246 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1056/NEJMoa2508820 No description available

Phase 1 trial shows potential for rezatapopt, a p53 reactivator, in treating TP53 Y220C-mutated tumors over a 21-day cycle. Exciting prospects! PMID:41740031, N Engl J Med 2026, @NEJM https://doi.org/10.1056/NEJMoa2508820 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1001/jamaneurol.2026.0240 No description available

A study in JAMA Neurology finds high EBV-derived EBNA-1 antibody titers could help distinguish MS from MOGAD and NMOSD. PMID:41801194, JAMA Neurol 2026, @JAMANeuro https://doi.org/10.1001/jamaneurol.2026.0240 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Identification of an allosteric site on the E3 ligase adapter cereblon | Nature Cereblon (CRBN) is the target of thalidomide derivatives1 that achieve therapeutic efficacy against some haematologic neoplasias2–4 by recruiting neosubstrates for degradation5–7. Despite the intense investigation of orthosteric thalidomide derivatives, little is known about alternate binding sites on CRBN. Here we report an evolutionarily conserved cryptic allosteric binding site on CRBN. Small-molecule SB-405483 binds the allosteric site to cooperatively enhance the binding of orthosteric ligands and alter their neosubstrate degradation profiles. A survey of over 100 orthosteric ligands and their degradation targets reveals trends in the classes of compounds and neosubstrates in which degradation outcomes are enhanced or inhibited by SB-405483. Structural investigations provide a mechanistic basis for the effects of the allosteric ligand by shifting the conformational distribution of CRBNopen to a novel CRBNint and increasing the CRBNclosed state. The discovery of a cryptic allosteri

Discovery: Cereblon has a conserved allosteric site. SB-405483 binds there, boosting function. Key for new therapeutic strategies beyond thalidomide derivatives. PMID:41565821, Nature 2026, @Nature https://doi.org/10.1038/s41586-025-09994-w #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1001/jamapsychiatry.2025.4638 No description available

Study predicts which adolescents benefit from school mindfulness via baseline traits; crucial step as depression starts young. PMID:41706471, JAMA Psychiatry 2026, @JAMAPsych https://doi.org/10.1001/jamapsychiatry.2025.4638 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1001/jamaneurol.2026.0072 No description available

A pilot RCT at Univ. of Pittsburgh studied low-dose lithium7 for MCI. It assessed cognition & biomarkers. Feasible & safe! PMID:41770546, JAMA Neurol 2026, @JAMANeuro https://doi.org/10.1001/jamaneurol.2026.0072 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Wait a second, why is atovaquone only available in that gross yellow liquid, but atovaquone-proguanil is in tablet form?? #IDsky #PharmSky

https://doi.org/10.1126/science.aec0173 No description available

New policies can boost diagnostic innovation. Investments could address 90% of global disease burden, impacting millions worldwide. PMID:41955384, Science 2026, @ScienceMagazine https://doi.org/10.1126/science.aec0173 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1056/NEJMoa2600752 No description available

Setidegrasib (ASP3082) tested for KRAS G12D involvement: targets NSCLC (5%) & pancreatic cancer (40%). Phase 1 study examined safety & efficacy. PMID:41879829, N Engl J Med 2026, @NEJM https://doi.org/10.1056/NEJMoa2600752 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Gabapentinoids found to increase risk of drug toxicity Study results have suggested that patients who take gabapentinoids are at greater risk of drug toxicity if they are also taking another medication. Publishing their findings in PLoS Medicine on 16 Apr...

#Medsky🧪 #Pharmsky #publichealth study found that patients taking gabapentinoids with benzodiazepines were at double the risk of being hospitalised with drug poisoning, while combining the drug with opioids has a 30% increase in risk.
pharmaceutical-journal.com/article/news...

Elucidating genetic backgrounds of myasthenia gravis in Japanese by genome-wide association studies and multi-omics analyses of thymoma | Nature Communications Myasthenia gravis (MG) is an autoimmune disorder characterized by impaired neuromuscular transmission and motor symptoms. Its genetic background remains unclear, particularly beyond specific subtypes reported in European populations. Here, we perform a genome-wide association study (GWAS) of 1,434 MG cases covering all disease subtypes and 42,913 controls of Japanese, which newly identify the TERT locus (odds ratio [OR] = 1.31, P = 1.7×10-10). Subtype-stratified GWASs show stronger signals for generalized MG (gMG; OR = 1.38, P = 1.6×10-12), anti AChR antibody-positive gMG (g-AChR-Ab(+)MG; OR= 1.49, P = 2.1×10-15), and thymoma-associated gMG (g-TAMG; OR = 1.92, P = 1.1×10-15). Fine-mapping of the major histocompatibility complex region reveal distinct associations of HLA-DRB1 with late onset gMG (g-LOMG) and HLA-A with early onset gMG (g-EOMG). The MG risk TERT lead variant rs2736099 is associated with poor treatment response, especially in g-AChR-Ab(+)MG and g-EOMG (P < 0.0042). The

Genome-wide study of 1,434 Japanese MG cases reveals TERT locus (OR=1.31, P=1.7x10^-10) as key. This insight could reshape MG treatment strategies. PMID:41820352, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-70376-5 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Looking forward to seeing you at this exciting
ESCMID Late-breaking session on Sunday
👇👇

@escmid.bsky.social @cmijournal.bsky.social @cmicomms.bsky.social @unmc-id.bsky.social #IDSky #MedSky #PCCSky #ICUSky #EMIMCC #Ansky #EMSky #AMSSky #TxID #meded #Pharmsky #Pharmed #RXSky #MicroSky #ClinMicro

https://doi.org/10.1038/s41556-026-01896-x No description available

Discover the mitochondrial transfer network between Leydig cells and testicular macrophages crucial for testosterone synthesis!🔥💡 PMID:41760931, Nat Cell Biol 2026, @NatureCellBio https://doi.org/10.1038/s41556-026-01896-x #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1038/s41556-026-01879-y No description available

Tumor acidosis induces a CS-enriched glycocalyx, enhancing lipid scavenging and resisting ferroptosis. Exciting insights! PMID:41673170, Nat Cell Biol 2026, @NatureCellBio https://doi.org/10.1038/s41556-026-01879-y #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1001/jamapsychiatry.2026.0037 No description available

A JAMA Psychiatry review links climate-related, nature-based interventions to improved mental health outcomes, analyzing SRMAs. PMID:41779404, JAMA Psychiatry 2026, @JAMAPsych https://doi.org/10.1001/jamapsychiatry.2026.0037 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Doing a pharmacy epic update this week with a lot of spreadsheets with every iteration of every drug and learned the brand name for flurbiprofen is "Ansaid".

I know there a bunch of med names like that, maybe the most on the nose brand name ever?

#pharmsky

https://doi.org/10.1038/s41581-026-01073-1 No description available

Air pollution & extreme temps harm kidneys! 🚨 Studies reveal PM₂.₅ & PM₁₀ pollutant dangers, tapping into ignored health realms. 🌍💧 PMID:41957144, Nat Rev Nephrol 2026, @NatRevNeph https://doi.org/10.1038/s41581-026-01073-1 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Metabolic masqueraders of paediatric and adult rheumatic diseases | Nature Reviews Rheumatology Inborn errors of metabolism comprise a clinically diverse group of conditions that arise from the decreased activity of an enzyme or metabolite transporter and subsequent blockade in a metabolic pathway. These disorders are typically considered in the differential diagnosis of critically ill neonates or young children presenting with hypoglycaemia, metabolic acidosis or hyperammonaemia. However, beyond these classic presentations, a broader group of inborn errors of metabolism can manifest more subtly, with progressive articular and multi-systemic involvement that mimics or overlaps with typical features of rheumatological disease. Consequently, these conditions might be misdiagnosed for years as rheumatological diseases, including juvenile idiopathic arthritis, systemic sclerosis, idiopathic inflammatory myopathies and systemic lupus erythematosus. Moreover, these disorders provide unique opportunities to understand the complex interplay between metabolism and immune function. With th

Metabolic disorders often mimic rheumatic diseases in children & adults, beyond neonatal issues like hypoglycaemia. PMID:41741762, Nat Rev Rheumatol 2026, @NatRevRheumatol https://doi.org/10.1038/s41584-026-01352-y #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1038/s41589-025-02131-8 No description available

Mutant IDH1-R132H undergoes autopalmitoylation at C269, enhancing its cancer-driving activity by producing (R)-2HG metabolite. PMID:41530531, Nat Chem Biol 2026, @nchembio https://doi.org/10.1038/s41589-025-02131-8 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

#Medsky🧪 #IDsky #pharmsky #publichealth #Carbapenemantibiotics are extensively employed in the treatment of severe bacterial infections due to their broad-spectrum activity and potent bactericidal effects, often serving as a last-line therapeutic option.

Atypical protein kinase C activation drives intestinal glucose excretion in diabetes mellitus | Nature Communications Intestinal glucose excretion, defined as increased intestinal serum glucose uptake and secretion into the lumen, influences bariatric surgery-associated glycaemic control. Here, we investigate molecular mechanisms that activate intestinal glucose excretion. We evaluate altered transcriptomes in variable intestinal glucose excretion models and big data-based drug discovery systems. We show that protein kinase C (PKC) activation mimics transcriptome alterations observed during intestinal glucose excretion. Among PKC subfamilies, atypical PKC (aPKC) facilitates glucose transporter 1 (GLUT1)-mediated intestinal glucose excretion without inducing oncogenic proliferation. Intestinal aPKC activation via transposon expression vector induces serum glucose uptake into intestinal tissues and excretion into the lumen. Prostratin, a non-tumorigenic phorbol ester, activates aPKC and induces a similar effect on intestinal glucose excretion. We identify the prostratin and aPKC/GLUT1 signalling pathway

PKC activation in diabetes drives intestinal glucose excretion, revealing a potential pathway for glycaemic control interventions post-bariatric surgery. PMID:41651859, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-69193-7 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

PUTT members are proud to stand alongside Congresswoman Harshbarger and Congressman Auchincloss who are true champions for #PBMreform and patient-first policies. Together, we're pushing for transparency, accountability, and a fairer future for independent pharmacies & their patients. #pharmsky

Announcing the ASPET Leadership Academy! Make sure you're ready for a leadership position with this webinar series, dedicated to preparing health sciences professionals for leadership roles. Learn more and register: https://ow.ly/QrMi50YIg36

#pharmsky 🧪

https://www.cell.com/cell/fulltext/S0092-8674(26)00162-5 No description available

Efficiency in clearing amyloid-β (Aβ) in Alzheimer's is enhanced by SPYTACs, a new eTPD platform, offering a safer alternative to anti-Aβ immunotherapy. PMID:41785850, Cell 2026, @Cell www.cell.com/cell/fulltext/S0092-8674... #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

The ubiquitin ligase KLHL6 drives resistance to CD8+ T cell dysfunction | Nature The multifaceted dysfunction of tumour-infiltrating T cells, including exhaustion and mitochondrial dysfunction, remains a major obstacle in cancer immunotherapy1–6. Transcriptomic and epigenomic regulation of T cell dysfunction have been extensively studied7–9, but the role of proteostasis in regulating these obstacles remains less defined. Here we combined computational analyses of atlases of T cell exhaustion and mitochondrial fitness with performed targeted in vivo CRISPR screens, which identified the E3 ubiquitin ligase KLHL6 as a dual-negative regulator of both T cell exhaustion and mitochondrial dysfunction. Mechanistically, KLHL6 expression promoted TOX poly-ubiquitination and subsequent proteasomal degradation, thereby attenuating the transition of progenitor exhausted T cells towards terminal exhaustion. Simultaneously, KLHL6 maintained mitochondrial fitness by constraining the excessive mitochondrial fission that occurs during chronic T cell receptor stimulation by means of

KLHL6's role as a ubiquitin ligase complicates T cell dysfunction, contributing to cancer therapy resistance, impacting CD8+ infiltrates. PMID:41535474, Nature 2026, @Nature @OTSociety @NAR_Open https://doi.org/10.1038/s41586-025-09926-8 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

https://doi.org/10.1056/NEJMra2415650 No description available

Cardiac resynchronization therapy enhances heart failure outcomes with LVEF ≤50%, utilizing biventricular pacing and wide QRS. Tested in 10k+ patients! PMID:41564398, N Engl J Med 2026, @NEJM https://doi.org/10.1056/NEJMra2415650 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Are you ready to take an active role in shaping the future of pharmacology and toxicology? Drug Metabolism and Disposition is seeking a new Editor-in-Chief. Learn more about the position and application: https://dmd.aspetjournals.org/news
#pharmsky 🧪