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New articles from Prof. David C. Rubinsztein, our Honorary Editor-in-Chief

Published on: 8 Dec 2021 Viewed: 382

On November 16, 2021, Clarivate Analytics announced the list of "Highly Cited Researchers 2021". Prof. David C. Rubinsztein, our Honorary Editor-in-Chief, is on the list. This week, we would like to share several latest articles from Prof. David C. Rubinsztein.

Title:  Vinexin contributes to autophagic decline in brain ageing across species
Authors: So Jung Park, Rebecca A. Frake, Cansu Karabiyik, Sung Min Son, Farah H. Siddiqi, Carla F. Bento, Peter Sterk, Mariella Vicinanza, Mariana Pavel,David C. Rubinsztein
Type: Article of Cell Death & Differentiation
Autophagic decline is considered a hallmark of ageing. The activity of this intracytoplasmic degradation pathway decreases with age in many tissues and autophagy induction ameliorates ageing in many organisms, including mice. Autophagy is a critical protective pathway in neurons and ageing is the primary risk factor for common neurodegenerative diseases. Here, we describe that autophagosome biogenesis declines with age in mouse brains and that this correlates with increased expression of the SORBS3 gene (encoding vinexin) in older mouse and human brain tissue. We characterise vinexin as a negative regulator of autophagy. SORBS3 knockdown increases F-actin structures, which compete with YAP/TAZ for binding to their negative regulators, angiomotins, in the cytosol. This promotes YAP/TAZ translocation into the nucleus, thereby increasing YAP/TAZ transcriptional activity and autophagy. Our data therefore suggest brain autophagy decreases with age in mammals and that this is likely, in part, mediated by increasing levels of vinexin.
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Title: Autophagy in major human diseases
Authors: Daniel J Klionsky, Giulia Petroni, Ravi K Amaravadi, Eric H Baehrecke, Andrea Ballabio, Patricia Boya, José Manuel Bravo-San Pedro, Ken Cadwell, Francesco Cecconi, Augustine M K Choi, Mary E Choi, Charleen T Chu, Patrice Codogno, Maria Isabel Colombo, Ana Maria Cuervo, Vojo Deretic, Ivan Dikic, Zvulun Elazar, Eeva-Liisa Eskelinen, Gian Maria Fimia, David A Gewirtz, Douglas R Green, Malene Hansen, Marja Jäättelä, Terje Johansen, Gábor Juhász, Vassiliki Karantza, Claudine Kraft, Guido Kroemer, Nicholas T Ktistakis, Sharad Kumar, Carlos Lopez-Otin, Kay F Macleod, Frank Madeo, Jennifer Martinez, Alicia Meléndez, Noboru Mizushima, Christian Münz, Josef M Penninger, Rushika M Perera, Mauro Piacentini, Fulvio Reggiori, David C Rubinsztein, Kevin M Ryan, Junichi Sadoshima, Laura Santambrogio, Luca Scorrano, Hans-Uwe Simon, Anna Katharina Simon, Anne Simonsen, Alexandra Stolz, Nektarios Tavernarakis, Sharon A Tooze, Tamotsu Yoshimori, Junying Yuan, Zhenyu Yue, Qing Zhong, Lorenzo Galluzzi, Federico Pietrocola
Type: Review of The EMBO Journal
Autophagy is a core molecular pathway for the preservation of cellular and organismal homeostasis. Pharmacological and genetic interventions impairing autophagy responses promote or aggravate disease in a plethora of experimental models. Consistently, mutations in autophagy-related processes cause severe human pathologies. Here, we review and discuss preclinical data linking autophagy dysfunction to the pathogenesis of major human disorders including cancer as well as cardiovascular, neurodegenerative, metabolic, pulmonary, renal, infectious, musculoskeletal, and ocular disorders.
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Title: The pleiotropic roles of autophagy in Alzheimer’s disease: From pathophysiology to therapy
Authors: Beatrice Paola Festa, Antonio Daniel Barbosa, Matea Rob, David C. Rubinsztein
Type: Review of Current Opinion in Pharmacology
Autophagy is a lysosomal degradation pathway and the main clearance route of many toxic protein aggregates. The molecular pathology of Alzheimer’s disease (AD) manifests in the form of protein aggregates—extracellular amyloid-β depositions and intracellular tau neurofibrillary tangles. Perturbations at different steps of the autophagy pathway observed in cellular and animal models of AD might contribute to amyloid-β and tau accumulation. Increased levels of autophagosomes detected in patients’ brains suggest an alteration of autophagy in human disease. Autophagy is also involved in the fine-tuning of inflammation, which increases in the early stages of AD and possibly drives its pathogenesis. Mounting evidence of a causal link between impaired autophagy and AD pathology uncovers an exciting opportunity for the development of autophagy-based therapeutics.
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Title: Autophagy in healthy aging and disease
Authors: Yahyah Aman, Tomas Schmauck-Medina, Malene Hansen, Richard I. Morimoto, Anna Katharina Simon, Ivana Bjedov, Konstantinos Palikaras, Anne Simonsen, Terje Johansen, Nektarios Tavernarakis, David C. Rubinsztein, Linda Partridge, Guido Kroemer, John Labbadia, Evandro F. Fang
Type: Review Article of Nature Aging
Autophagy is a fundamental cellular process that eliminates molecules and subcellular elements, including nucleic acids, proteins, lipids and organelles, via lysosome-mediated degradation to promote homeostasis, differentiation, development and survival. While autophagy is intimately linked to health, the intricate relationship among autophagy, aging and disease remains unclear. This Review examines several emerging features of autophagy and postulates how they may be linked to aging as well as to the development and progression of disease. In addition, we discuss current preclinical evidence arguing for the use of autophagy modulators as suppressors of age-related pathologies such as neurodegenerative diseases. Finally, we highlight key questions and propose novel research avenues that will likely reveal new links between autophagy and the hallmarks of aging. Understanding the precise interplay between autophagy and the risk of age-related pathologies across organisms will eventually facilitate the development of clinical applications that promote long-term health.
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Title: Transient siRNA-mediated protein knockdown in mouse followed by feeding/starving cycle and liver tissue analysis
Authors: Lidia Wrobel, Farah H.Siddiqi, David C.Rubinsztein
Type: Protocol of STAR Protocols

  • siRNA-mediated knockdown of a gene of interest in mouse liver
  • Gene expression analysis at the mRNA and protein levels in the liver tissue
  • Fasting/refeeding response at the mRNA and protein levels in the liver tissue

We present a protocol for in vivo siRNA-mediated knockdown of a gene of interest in mouse liver using systemic delivery via intravenous injection. We describe a step-by-step protocol for delivery of siRNA particles, with tips on how to optimize dosage. We detail steps for feeding/starving cycles as well as for liver tissue isolation, followed by gene expression analysis, measured at the mRNA and protein levels.
For complete information on the generation and use of this protocol, please refer to Wrobel et al. (2020).
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