Article
Multidisciplinary Sciences
Gihan P. Ruwanpathirana, Robert C. Williams, Colin L. Masters, Christopher C. Rowe, Leigh A. Johnston, Catherine E. Davey
Summary: The molecular mechanism of intracellular tau accumulation caused by extracellular A beta-amyloid (A beta) in Alzheimer's disease is not well understood. This study used a convolutional neural network (CNN) to analyze the association between A beta and tau, revealing new associations. The CNN accurately predicted the relationship between A beta and tau.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Rawan Tarawneh
Summary: Alzheimer's disease (AD) models propose that abnormal protein aggregation is the primary event in AD, but recent evidence indicates that reduced blood flow due to capillary loss and endothelial dysfunction may be the early and primary events in AD pathogenesis. These vascular factors may precede amyloid and tau aggregation and contribute to neuronal and synaptic injury. Clinical studies have shown that endothelial dysfunction is closely related to cognitive outcomes in AD, suggesting that promoting endothelial repair in early AD may be a potential therapeutic strategy to slow disease progression. This review examines evidence from various studies supporting the vascular hypothesis of AD and emphasizes the need for further investigations into its role in the disease.
Review
Biochemistry & Molecular Biology
Patrik Oleksak, Michal Novotny, Jiri Patocka, Eugenie Nepovimova, Jakub Hort, Jan Pavlik, Blanka Klimova, Martin Valis, Kamil Kuca
Summary: Scientists are searching for new approaches to improve symptoms of Alzheimer's disease, with cevimeline showing potential in improving cognitive functions and influencing disease pathology. Further clinical studies are needed to confirm and extend these findings before it can be approved for use among AD patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Thomas S. Webberley, Ryan J. Bevan, Joshua Kerry-Smith, Jordanna Dally, Daryn R. Michael, Sophie Thomas, Meg Rees, James E. Morgan, Julian R. Marchesi, Mark A. Good, Sue F. Plummer, Duolao Wang, Timothy R. Hughes
Summary: This study assessed the neuroprotective potential of the Lab4P probiotic consortium in aging and metabolic syndrome-associated neurodegenerative pathologies. The results showed that supplementation with probiotics prevented cognitive decline, hippocampal neuron deterioration, and inflammation in mice. In human cell culture models, probiotic metabolites demonstrated a neuroprotective capability against beta-amyloid challenge. Overall, these findings suggest that Lab4P has the potential to be a neuroprotective agent and support further research in other neurodegenerative conditions in animal models and human studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Cell Biology
Xufeng Cen, Xiaoyan Xu, Hongguang Xia
Summary: This study identified a small molecule compound, UMI-77, as a safe and effective inducer of mitophagy to improve cognitive decline in an AD mouse model. It sheds light on novel mechanisms of mitophagy, demonstrates MCL1 as a receptor that can be targeted to induce mitophagy, and identifies MCL1 as a drug target for therapeutic intervention in AD.
Article
Biochemistry & Molecular Biology
Stefan Wendt, Sora Johnson, Nicholas L. Weilinger, Christopher Groten, Stefano Sorrentino, Jonathan Frew, Lucy Yang, Hyun B. Choi, Haakon B. Nygaard, Brian A. MacVicar
Summary: The inter-relationship between microglia dynamics and oxidative stress in dystrophic neurites at Alzheimer's Disease plaques may contribute to the pathological changes in neurons. Microglia preferentially enwrap neurites exhibiting the greatest degree of oxidative stress, and depletion of microglia leads to increased oxidative stress in neurites. These findings suggest a complex role of microglia in Alzheimer's Disease, with both neuroprotective and neurotoxic components.
Article
Neurosciences
Hui-Ru Bi, Cui-Hua Zhou, Yi-Zhi Zhang, Xu-Dong Cai, Mu-Huo Ji, Jian-Jun Yang, Gui-Quan Chen, Yi-Min Hu
Summary: Pen-2 is essential for neuronal survival in the adult cerebral cortex, and its loss results in astrocytosis, cortical atrophy, neuronal loss, as well as microgliosis and enhanced inflammatory responses in the cortex. The Notch signaling pathway does not appear to be involved in the neurodegeneration caused by the loss of Pen-2.
CNS NEUROSCIENCE & THERAPEUTICS
(2021)
Review
Biochemistry & Molecular Biology
Eleonora Ficiara, Zunaira Munir, Silvia Boschi, Maria Eugenia Caligiuri, Caterina Guiot
Summary: Proper functioning of all organs, including the brain, requires iron, which is present in different forms in biological fluids. Clinical parameters for monitoring iron concentration in biological fluids may not detect circulating iron accurately, while indirect measurements like magnetic resonance imaging need further validation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Endocrinology & Metabolism
Teresa Juarez-Cedillo, Evangelina Gonzalez-Figueroa, Nancy Martinez-Rodriguez, Jose M. Fragosos, Osvaldo Garrido-Acosta, Gilberto Vargas-Alarcon
Summary: The study found significant effects of COMT Val/Met, Val/Val genotype polymorphisms on cognitive performance, suggesting potential new therapeutic targets for dementia-related cognitive impairment. Other risk genotypes or haplotypes need to be further evaluated for their association with cognitive decline in dementia.
METABOLIC BRAIN DISEASE
(2021)
Article
Medicine, General & Internal
Luisa Agnello, Bruna Lo Sasso, Matteo Vidali, Concetta Scazzone, Caterina Maria Gambino, Tommaso Piccoli, Giulia Bivona, Anna Maria Ciaccio, Rosaria Vincenza Giglio, Vincenzo La Bella, Marcello Ciaccio
Summary: This study evaluated cerebrospinal fluid (CSF) alpha-syn levels in different neurological disorders, showing that patients with Parkinson's Disease (PD) had the lowest levels while patients with Alzheimer's Disease (AD) had the highest levels. In AD patients, alpha-syn levels were significantly associated with tau proteins, suggesting alpha-syn could serve as a biomarker for neurodegenerative diseases.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Alejandro Quintero-Villegas, Sergio Ivan Valdes-Ferrer
Summary: 5-HT7 receptors are the most recently identified among serotonin receptors, and their role in neurodegenerative diseases is not fully understood. This review discusses the signaling pathways and cellular mechanisms involved in 5-HT7R activation, as well as the potential therapeutic implications of pharmacological interventions for 5-HT7R signaling in neurodegeneration.
MOLECULAR MEDICINE
(2022)
Article
Clinical Neurology
Anuschka Silva-Spinola, Marisa Lima, Maria Joao Leitao, Catarina Bernardes, Joao Duraes, Diana Duro, Miguel Tabuas-Pereira, Isabel Santana, Ines Baldeiras
Summary: This study evaluated the potential of peripheral neurological biomarkers to predict progression to Alzheimer's disease in patients with mild cognitive impairment (MCI), and examined the relationship between blood and cerebrospinal fluid (CSF) markers. The results showed that levels of NfL, GFAP, and p-Tau181 in the blood were significantly higher in patients who progressed to Alzheimer's disease. Combining blood-based GFAP, NfL, and p-Tau181 may serve as a prognostic tool for MCI.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Review
Geriatrics & Gerontology
Yun Wei, Xianxiao Li
Summary: Microglia, immune-competent cells, play a critical role in maintaining normal brain function. In Alzheimer's disease, microglial proliferation and activation occur around amyloid plaques. Recent research has discovered various microglial phenotypes related to aging and Alzheimer's disease, beyond the traditional M1 and M2 types. Redox signaling regulates the acquisition of different microglial activation phenotypes, which are associated with distinct molecular signatures.
Review
Neurosciences
Karra D. Harrington, Shradha Vasan, Jee Eun Kang, Martin J. Sliwinski, Michelle H. Lim
Summary: This systematic review and meta-analysis examined the relationship between loneliness and cognitive function, showing that loneliness is associated with subtle impairment across multiple cognitive domains in older adults. These findings are important for understanding how loneliness affects cognitive function and providing valuable information for risk reduction and early detection strategies.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Plant Sciences
Jing-Tian Zhang, Li -Ya Xie, Qiong Shen, Wei Liu, Ming -Han Li, Rui-Yi Hu, Jun-Nan Hu, Zi Wang, Chen Chen, Wei Li
Summary: This study investigated the regulatory effects of Platycodin D (PD) on neurodegeneration caused by reactive oxidative stress (ROS). In vivo and in vitro experiments demonstrated that PD could improve memory, reduce cell apoptosis and ROS production, and inhibit inflammation. PD enhanced the antioxidant ability by activating AMPK. This study suggests that PD may be a potential pharmaceutical agent to treat ROS-induced neurodegeneration.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Laia Carballo-Perich, Dolors Puigoriol-Illamola, Saima Bashir, Mikel Terceno, Yolanda Silva, Carme Gubern-Merida, Joaquin Serena
Summary: This study focuses on epigenetic biomarkers of carotid atherosclerosis and plaque vulnerability, proposing a better patient selection method and providing significant implications for accurate treatment of cardiovascular diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Sandra Codony, Caterina Pont, Christian Grinan-Ferre, Ania Di Pede-Mattatelli, Carla Calvo-Tusell, Ferran Feixas, Silvia Osuna, Julia Jarne-Ferrer, Marina Naldi, Manuela Bartolini, Maria Isabel Loza, Jose Brea, Belen Perez, Clara Bartra, Coral Sanfeliu, Jordi Juarez-Jimenez, Christophe Morisseau, Bruce D. Hammock, Merce Pallas, Santiago Vazquez, Diego Munoz-Torrero
Summary: The advent of multitarget drug discovery has brought hope for the treatment of multifactorial diseases. A new dual inhibitor has shown positive effects on neuroinflammation and memory impairment and exhibits favorable drug properties.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Cell Biology
Foteini Vasilopoulou, Aina Bellver-Sanchis, Julia Companys-Alemany, Julia Jarne-Ferrer, Alba Irisarri, Veronica Palomera-Avalos, Celia Gonzalez-Castillo, Daniel Ortuno-Sahagun, Coral Sanfeliu, Merce Pallas, Christian Grinan-Ferre
Summary: This study investigates the molecular mechanisms underlying the behavioural and psychological symptoms of dementia (BPSD) in Alzheimer's Disease (AD) patients. It suggests that epigenetic modulation, particularly through G9a methyltransferase and its histone mark (H3K9me2), plays a key role in shaping learning and memory. The study also reveals the association between increased levels of G9a, autophagic deficits, and alterations in synaptic plasticity, providing further understanding of the cognitive decline and BPSD exhibited by the AD model.
Article
Biochemistry & Molecular Biology
Clara Bartra, Lars Andre Jager, Anna Alcarraz, Aline Meza-Ramos, Gemma Sanguesa, Ruben Corpas, Eduard Guasch, Montserrat Batlle, Coral Sanfeliu
Summary: Physically active lifestyle has significant implications for the health and well-being, but excessive training can lead to cardiovascular events and impaired brain plasticity. In this study, young adult male mice were subjected to moderate or high-intensity treadmill running for eight weeks. The high-intensity training resulted in decreased weight gain and cardiac hypertrophy, but without hemodynamic overload. It also reduced heart rate and improved motor skills, without impairing recognition or spatial memory.
Review
Clinical Neurology
Mikel Terceno, Saima Bashir, Juan Cienfuegos, Alan Murillo, Victor Augusto Vera-Monge, Laura Pardo, Montserrat Reina, Carme Gubern-Merida, Dolors Puigoriol-Illamola, Laia Carballo, Anna Costa, Maria Buxo, Joaquin Serena, Yolanda Silva
Summary: The optimal choice of anesthetic approach in endovascular treatment of posterior circulation large vessel occlusion (PC-LVO) strokes is still unclear. This meta-analysis compared conscious sedation (CS) and general anesthesia (GA) and found that CS was associated with better clinical outcomes and lower mortality at 3 months. However, there were no significant differences in final reperfusion rates and procedural duration.
EUROPEAN STROKE JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Clara Bartra, Alba Irisarri, Ainhoa Villoslada, Ruben Corpas, Samuel Aguirre, Elisa Garcia-Lara, Cristina Sunol, Merce Pallas, Christian Grinan-Ferre, Coral Sanfeliu
Summary: Maternal treatment with TPPU during gestation and lactation can prevent or delay memory loss and AD pathology, possibly by modulating the brain's epigenetic machinery and marks.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Amanda Cano, Alvaro Munoz-Morales, Elena Sanchez-Lopez, Miren Ettcheto, Eliana B. Souto, Antonio Camins, Merce Boada, Agustin Ruiz
Summary: Neurodegenerative diseases have unknown etiology in many cases and lack effective treatments. The blood-brain barrier poses a challenge for drug delivery. Exosomes, secreted vesicles, have emerged as promising therapeutic tools due to their natural origin and molecular similarities. They are particularly promising for targeting neurodegenerative diseases due to the difficulty of accessing the brain and the complexity of the diseases.
Article
Pharmacology & Pharmacy
Ruth M. Galindo-Camacho, Isabel Haro, Maria J. Gomara, Marta Espina, Joel Fonseca, Carlos Martins-Gomes, Antoni Camins, Amelia M. Silva, Maria L. Garcia, Eliana B. Souto
Summary: The biocompatibility of cell penetrating peptides-functionalized Licochalcone-A-loaded PLGA nanoparticles was evaluated in Caco-2 cell lines, demonstrating non-cytotoxicity, while the anti-inflammatory activity of the nanoparticles was tested in RAW 264.7 cell lines. Freeze-drying with different cryoprotectants was performed to prevent particle aggregation and physical stress. An in-situ forming gel based on poloxamer 407 containing Licochalcone-A-loaded PLGA nanoparticles functionalized with B6 and Tet-1 was developed for ocular administration, providing viscoelasticity, suitable mechanical properties, and mucoadhesive performance.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Abhisek Jana, Rahul Naga, Sougata Saha, Christian Grinan-Ferre, Deb Ranjan Banerjee
Summary: In this study, a new natural lead against Protein Lysine Methyltransferase 2 (EHMT2/G9a) was identified using a blended ligand and structure-based pharmacophore screening approach. EHMT2/G9a is associated with cancer, Alzheimer's, and aging, and is considered an emerging drug target. Two pharmacophores, based on the common features of known inhibitors and the interaction profile of crystal structures, were developed and validated. These pharmacophores were used in combination to screen over 741,543 compounds. The screening process also included tests for drug-likeness and toxicity, and the potential inhibitors were further analyzed through docking, simulation, and comparative analysis.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biophysics
Gerard Esteruelas, Alba Ortiz, Josefina Prat, Estefania Vega, Montserrat Munoz-Juncosa, Maria Luisa Garcia Lopez, Miren Ettcheto, Antoni Camins, Elena Sanchez-Lopez, Montserrat Pujol
Summary: Ocular inflammation is commonly treated using nonsteroidal anti-inflammatory drugs. Encapsulating these drugs into PLGA nanoparticles allows for better bioavailability. This study investigates the interaction of Dexibuprofen (DXI) nanoparticles with corneal membranes and finds differences in interactions between elder and adult corneal tissues.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2023)
Review
Biochemistry & Molecular Biology
Jordi Olloquequi, Miren Ettcheto, Amanda Cano, Ana Fortuna, Joana Bicker, Elena Sanchez-Lopez, Cristian Paz, Jesus Urena, Ester Verdaguer, Carme Auladell, Antoni Camins
Summary: Licochalcone A (Lico-A) is a potential neuroprotective agent with various mechanisms of action, including enhancing cognitive activity, inhibiting neuroinflammation, reducing tau phosphorylation, increasing acetylcholine levels, decreasing amyloid plaques, and exerting antioxidant effects. Further research on the underlying mechanisms and targets of Lico-A may provide new insights for the treatment of cognitive disorders and neurodegenerative diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Abhisek Jana, Aina Bellver-Sanchis, Christian Grinan-Ferre, Deb Ranjan Banerjee
Summary: In this study, we report for the first time the inhibition of G9a/EHMT2 and the anti-Alzheimer's activities of the drug raltitrexed. Raltitrexed inhibits G9a directly and reduces the levels of H3K9me2/ H3K9 in an AD transgenic worm model. Furthermore, raltitrexed exhibits a safe toxicity/function range and enhances locomotive function in worms, while reducing amyloid beta aggregates.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Pharmacology & Pharmacy
Andrea Bagan, Sergio Rodriguez-Arevalo, Teresa Taboada-Jara, Christian Grinan-Ferre, Merce Pallas, Iria Brocos-Mosquera, Luis F. Callado, Jose A. Morales-Garcia, Belen Perez, Caridad Diaz, Rosario Fernandez-Godino, Olga Genilloud, Milan Beljkas, Slavica Oljacic, Katarina Nikolic, Carmen Escolano
Summary: This study aims to find molecular entities that modulate imidazoline I-2 receptors (I-2-IRs) as potential therapeutic targets for Alzheimer's disease. The findings demonstrate that the new I-2-IR ligands have beneficial effects in neuroprotection, anti-inflammation, and improvement of cognitive impairment, suggesting their potential as a promising therapeutic strategy for neurodegenerative diseases.
Review
Biochemistry & Molecular Biology
Rebeca Perez, Viviana Burgos, Victor Marin, Antoni Camins, Jordi Olloquequi, Ivan Gonzalez-Chavarria, Henning Ulrich, Ursula Wyneke, Alejandro Luarte, Leandro Ortiz, Cristian Paz
Summary: Neurodegenerative disorders involve the progressive degeneration and death of neurons, and oxidative stress and neuroinflammation play crucial roles in their progression. Two major pathways, Nrf2 and NF-kappa B, have been identified as potential therapeutic targets due to their involvement in oxidative protection and the promotion of cytokine expression, respectively. Caffeic acid phenethyl ester (CAPE), a compound found in propolis, has shown neuroprotective activity by modulating these pathways. This review summarizes the biosynthesis and chemical synthesis of CAPE derivatives and discusses their neuroprotective activity in both in vitro and in vivo studies conducted from 2010 to 2023.
Article
Multidisciplinary Sciences
Saghar Rabieipoor, Meysam Zare, Miren Ettcheto, Antoni Camins, Mohammad Javan
Summary: This study evaluated the therapeutic effects of metformin in a mouse model of Alzheimer's disease. The results showed that metformin reduced inflammatory cells and reactive astrocytes as well as the dying neurons in the hippocampus region and the cortex, and improved cognitive performance.
