Article
Cell Biology
Hassan Elsana, Reut Bruck-Haimson, Huadong Zhu, Atif Ahmed Siddiqui, Adam Zaretsky, Irit Cohen, Hana Boocholez, Noa Roitenberg, Lorna Moll, Inbar Plaschkes, David Naor, Ehud Cohen
Summary: This study discovered that a small peptide called 5MER peptide, derived from human CD44 protein, can mitigate the toxicity of aggregative proteins associated with neurodegenerative disorders. The protection offered by the peptide is dependent on aging-regulating transcription factors and involves enhanced Aβ and polyQ35-YFP aggregation. The peptide modifies signaling pathways and gene expression, particularly those related to protein homeostasis, and activates transcellular chaperone signaling to promote proteostasis.
Article
Gastroenterology & Hepatology
David A. Rudnick, Jiansheng Huang, Tunda Hidvegi, Andrew S. Chu, Pamela Hale, Admire Munanairi, Dennis J. Dietzen, Paul F. Cliften, Eric Tycksen, Andrew J. Lutkewitte, Brian N. Finck, Stephen C. Pak, Gary A. Silverman, David H. Perlmutter
Summary: Insulin signaling exacerbates hepatic proteotoxicity in PiZ mice with alpha 1-antitrypsin deficiency, and PGC1 alpha is identified as a novel therapeutic target.
Article
Multidisciplinary Sciences
Eugenia Wulff-Fuentes, Jeffrey Boakye, Kaeley Kroenke, Rex R. Berendt, Carla Martinez-Morant, Michaela Pereckas, John A. Hanover, Stephanie Olivier-Van Stichelen
Summary: The study investigates the role of O-GlcNAcylation in regulating the solubility and aggregation of OTX2 protein, potentially preventing OTX2 aggregation through its interaction with CCT5 protein. Additionally, O-GlcNAc-depleted OTX2 is detrimental to cancer cells.
Article
Biochemistry & Molecular Biology
Eleni Panagiotidou, Anna Gioran, Daniele Bano, Niki Chondrogianni
Summary: Proteostasis reinforcement is vital in developing therapeutic interventions against proteinopathies, and understanding the mechanisms of its cell non-autonomous regulation is crucial. We demonstrate that proteasome activation in the nervous system can enhance proteasome activity in muscle, and this communication depends on Small Clear Vesicles and glutamate as a neurotransmitter. Importantly, this cell non-autonomous proteasome activation can prevent amyloid-beta (Aβ) mediated proteotoxic effects in muscle, but not resistance against oxidative stress. This identified distal communication may have significant implications in the design of tissue-specific proteasome manipulation strategies.
Article
Cell Biology
Bernd Bauer, Sascha Martens, Luca Ferrari
Summary: Cells maintain the functionality of their proteome through the proteostasis network, which includes chaperones, the ubiquitin-proteasome system, and autophagy. The decline of this network leads to protein aggregate accumulation and is associated with aging and disease. This article provides an overview of the molecular mechanisms of aggrephagy, a selective autophagy pathway for protein aggregate removal, including its regulation through post-translational modifications and auxiliary proteins. It also discusses alternative aggrephagy pathways in physiology and their disruption in pathology, particularly focusing on aggrephagy in neurons and protein aggregation in various diseases. Finally, strategies to reprogram aggrephagy for the treatment of protein aggregation diseases are highlighted.
JOURNAL OF CELL SCIENCE
(2023)
Article
Cell Biology
Eleni-Dimitra Papanagnou, Sentiljana Gumeni, Aimilia D. Sklirou, Alexandra Rafeletou, Evangelos Terpos, Kleoniki Keklikoglou, Efstathios Kastritis, Kimon Stamatelopoulos, Gerasimos P. Sykiotis, Meletios A. Dimopoulos, Ioannis P. Trougakos
Summary: The ubiquitin-proteasome pathway plays a crucial role in cell viability, especially in post-mitotic cells like cardiomyocytes. Dysfunction in heart-targeted proteasome activity can lead to disrupted cardiac activity, systemic toxicity, and reduced longevity. Activation of autophagy can partially rescue these phenotypes.
Review
Pharmacology & Pharmacy
Arun Upadhyay
Summary: The coordination of molecular mechanisms within cells is crucial for cellular function, and modulating the protein quality control system can alleviate cellular protein load and mitigate pathological conditions. Natural medicine and small molecule-based therapies have been shown to effectively restore cellular protein homeostasis for combating disease conditions.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Cell Biology
Ananth R. Srinivasan, Tracy T. Tran, Nancy M. Bonini
Summary: This study investigates the role of miR-34 in age-related phenotypes in the brain, finding that miR-34 regulates translation, protein aggregation, and autophagy. Additionally, the study suggests that miR-34 may target Lst8 and other genes involved in maintaining proteostasis and brain health.
Article
Neurosciences
Julia E. Gerson, Stephanie Sandoval-Pistorius, Jacqueline P. Welday, Aleija Rodriguez, Jordan D. Gregory, Nyjerus Liggans, Kylie Schache, Xingli Li, Hanna Trzeciakiewicz, Sami Barmada, Lisa M. Sharkey, Henry L. Paulson
Summary: Accumulation of tau protein is toxic in several neurodegenerative disorders. This study found that UBQLN2, a class of proteins linked to protein quality control and neurodegenerative diseases, plays a role in regulating tau protein. UBQLN2 can efficiently decrease wild-type tau levels regardless of aggregation, suggesting its involvement in tau regulation under normal conditions or early in disease. An imbalance of UBQLN2 disrupts ubiquitin-dependent protein quality control and autophagy, exacerbating neurodegeneration.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Medicine, Research & Experimental
Brigida R. Pinho, Liliana M. Almeida, Michael R. Duchen, Jorge M. A. Oliveira
Summary: The use of YM-1 can effectively modulate huntingtin protein proteostasis, reducing aggregation and enhancing degradation, making it a potential approach for treating Huntington's disease.
Review
Geriatrics & Gerontology
Haleh Barmaki, Alireza Nourazarian, Fatemeh Khaki-Khatibi
Summary: This review examines the impact of impaired autophagy on the progression of Alzheimer's disease pathology. Autophagy plays a crucial role in removing abnormal proteins and damaged organelles, but it weakens with aging and disease progression, leading to the accumulation of toxic proteins and neurodegeneration. There are therapeutic strategies to revitalize autophagy, but they face challenges in clinical practice.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Cell Biology
Marianna Kapetanou, Tobias Nespital, Luke S. Tain, Andre Pahl, Linda Partridge, Efstathios S. Gonos
Summary: As organisms age, proteostasis is disrupted, leading to the accumulation of damaged and aggregated proteins. The FoxO1 transcription factor is shown to directly regulate proteasome activity by controlling the expression of catalytic subunits, impacting longevity and protein homeostasis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Petra Wiedmer, Tobias Jung, Jose Pedro Castro, Laura C. D. Pomatto, Patrick Y. Sun, Kelvin J. A. Davies, Tilman Grune
Summary: Sarcopenia is a muscle-wasting syndrome characterized by progressive loss of skeletal muscle mass, quality, and strength during normal aging. Patients with sarcopenia mainly suffer from loss of muscle strength, leading to mobility disorders, increased risk of morbidity, and mortality. Various molecular mechanisms, including hormone function, muscle fiber composition, and inflammatory pathways, have been identified as causes of sarcopenia.
AGEING RESEARCH REVIEWS
(2021)
Review
Cell Biology
Cong Ma, Ronghui Yu, Junhong Li, Jiashuo Chao, Ping Liu
Summary: Osteoporosis is a common bone disease that increases bone fragility and susceptibility to fractures. With an aging population, it has become a growing public health problem. The pathogenesis of osteoporosis is still unclear, and effective interventions are limited. Therefore, exploring new targets for pharmacological interventions is of great clinical value.
AGEING RESEARCH REVIEWS
(2023)
Review
Cell Biology
Yuvraj Anandrao Jagtap, Prashant Kumar, Sumit Kinger, Ankur Rakesh Dubey, Akash Choudhary, Ravi Kumar Gutti, Sarika Singh, Hem Chandra Jha, Krishna Mohan Poluri, Amit Mishra
Summary: Disturbance in mitochondrial functions is a defining characteristic of neurodegenerative diseases, such as Parkinson's, ALS, and Alzheimer's. Misfolded proteins play a role in the impairment of mitochondrial pathways, exacerbating disease progression. However, the impact of mitochondrial dysfunction on other organelles and cellular processes remains understudied. Investigating the interplay between mitochondria and neurodegeneration can provide valuable insights for targeted therapies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)