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Cells

Cells is an international, peer-reviewed, open access journal on cell biology, molecular biology, and biophysics, published semimonthly online by MDPI.
The Nordic Autophagy Society (NAS), the Spanish Society of Hematology and Hemotherapy (SEHH) and the International Cell Death Society (ICDS) are affiliated with Cells and their members receive discounts on the article processing charges.
Indexed in PubMed | Quartile Ranking JCR - Q2 (Cell Biology)

All Articles (20,065)

p62/SQSTM1 is a multifunctional scaffold protein central to selective autophagy and, more recently, recognized as a regulator of ubiquitin–proteasome system-mediated degradation of intracellular proteins. Within phase-separated condensates, p62 has been shown to recruit and sequester the proteasome, yet the molecular basis for this interaction has remained largely unknown. Our previous study demonstrated that the ‘PB1’ domain (residues 1–123) of p62 is necessary for proteasome binding. However, this long stretch is also responsible for other functions of p62, such as condensate assembly and signal transduction. Thus, it was important to define more precisely the region responsible for interaction with the proteasome. In this study, we used systematic deletion variants of p62 and biochemical assays to delineate the minimal sequence within the PB1 domain responsible for proteasome binding. Our analyses revealed a small stretch of six amino acids (residues 84–89) that bind the proteasome and are distinct from the region responsible for condensate formation. Such a precise variant can serve as a useful tool to dissect how p62–proteasome interaction affects selective degradation and probably stress response, separating it from other p62 functions. Overall, this work advances our understanding of the structural determinants underlying p62’s dual role in autophagy and UPS regulation.

12 February 2026

Mapping of the PIR domain. (A) Immunofluorescence images of HeLa p62KO cells transfected with FLAG-tagged constructs: p62-PB1 (1–115), p62WT, and p62ΔPB1 (∆1–123). Cells were co-stained with antibodies against FLAG (green) and the proteasome α6 subunit (red). Scale bars: 20 μm. (B) Immunofluorescence images of HeLa p62KO cells expressing N-terminal deletion variants (Figure S1) of p62. Cells were co-stained for FLAG (green) and the proteasome α6 subunit (red). Scale bars: 30 μm. (C) (i) Immunofluorescence images of HeLa p62KO cells expressing RFP-tagged PB1 internal deletion variants. Cells were immunostained for the proteasome α6 subunit (green). Scale bars: 40 μm. (ii) Quantitative colocalization analysis between p62 variants and the proteasome. In all panels, arrows point to p62 foci.

A Rationally Designed AAV9-DM Capsid with Minimal Liver Tropism

  • Zoe C. Nabakowski,
  • Izabella C. Jaramillo and
  • Geoffrey D. Keeler
  • + 1 author

Adeno-associated viral vectors (AAV) are the leading gene therapy in the clinic. AAV9 has been of particular interest due to its wide tropism for multiple tissue types as well as being able to cross the blood-brain barrier and transduce central nervous system tissues. However, effectively and safely targeting extrahepatic tissue following the systemic administration of AAV9 remains a challenge due to high rates of liver transduction and liver toxicity. Thus, a crucial first step in developing a safe AAV9-based vector is to reduce liver targeting. Here we utilized rational design techniques to make five point mutations in the AAV9 capsid. In doing so, we developed a novel AAV9 variant, AAV9-DM, that is characterized by reduced liver tropism as compared to AAV9 and other liver de-targeted AAV9 mutants. We show that AAV9-DM is effective at transducing cells in vivo, resulting in robust transgene expression over a 9-week period. Importantly, the AAV9-DM capsid maintains the ability to transduce non-hepatic tissues with a biodistribution similar to AAV9. This new mutant represents a novel AAV capsid that may be the basis for developing safer therapeutics to target extrahepatic tissue while reducing adverse side effects related to liver transduction.

12 February 2026

Pulmonary Arterial Hypertension: Reconfiguring the Vascular Landscape to Reverse Remodeling

  • Alice G. Vassiliou,
  • Kostas A. Papavassiliou and
  • Athanasios G. Papavassiliou
  • + 2 authors

The therapeutic interventions for pulmonary arterial hypertension (PAH) have predominantly focused on facilitating pulmonary blood flow by inducing vasodilation to reduce the mechanical resistance against the right ventricle (RV) [...]

11 February 2026

Headache disorders, including migraine, tension-type headache, trigeminal autonomic cephalalgias, post-traumatic headache and medication overuse headache, represent a major global health burden and remain difficult to treat despite therapeutic advances. The endocannabinoid system (ECS) has emerged as a key regulator of neural, vascular, and immune processes central to headache pathophysiology. Through coordinated actions of CB1 and CB2 receptors, the endogenous ligands anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and their metabolic enzymes, the ECS modulates trigeminovascular activity, descending pain control, cortical excitability, and neuroimmune sensitization. Preclinical studies demonstrate that ECS activation suppresses trigeminal firing, reduces calcitonin gene-related peptide (CGRP) release, attenuates neurogenic inflammation, stabilizes cortical susceptibility to spreading depression, and limits glial activation following traumatic brain injury. Conversely, ECS dysregulation contributes to central sensitization and impaired descending inhibition underlying medication overuse headache and other headache disorders. Pharmacological strategies targeting endocannabinoid degradation, such as inhibition of FAAH, MAGL, and COX-2, enhance endogenous cannabinoid tone and consistently reduce headache-like behaviors across diverse models. Importantly, sex differences shape ECS function, with females exhibiting distinct hormonal regulation, receptor expression, and glial activation that influence responsiveness to ECS-targeted interventions. Collectively, mechanistic and translational evidence highlights the ECS as a promising therapeutic target across primary and secondary headache disorders. Future clinical studies should incorporate sex-informed designs, integrate biomarkers of trigeminovascular and neuroimmune activity, and evaluate peripherally restricted ECS modulators and cannabinoid-based formulations as candidates for individualized headache therapy.

11 February 2026

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Editors: Vasso Apostolopoulos, Jack Feehan, Vivek P. Chavda
Cellular and Molecular Mechanisms in Immune Regulation
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Editors: Fábio Rinaldo Santori, Natalia B. Ivanova

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Cells - ISSN 2073-4409