Review
Biochemistry & Molecular Biology
Anamaria Jurcau
Summary: Huntington's disease is an inherited neurodegenerative disease that primarily affects medium spiny neurons in the striatum. The mutant huntingtin protein leads to neuronal loss through a series of molecular cascades, involving excitotoxicity, transcriptional dysregulation, and other key factors. In addition to neurons, astrocytes are also dysfunctional due to the presence of mutant huntingtin, and neuroinflammation may further contribute to the pathogenesis of Huntington's disease.
Article
Cell Biology
Sandra Franco-Iborra, Ainhoa Plaza-Zabala, Marta Montpeyo, David Sebastian, Miquel Vila, Marta Martinez-Vicente
Summary: The study found that HTT protein plays a crucial role in mitophagy, and the expansion of its polyQ tract affects this process, ultimately leading to the accumulation of damaged mitochondria and an increase in oxidative stress, leading to negative effects on mitochondrial dysfunction and neurodegeneration in Huntington disease.
Article
Multidisciplinary Sciences
Thomas B. Layton, Lynn Williams, Nan Yang, Mingjun Zhang, Carl Lee, Marc Feldmann, Glenda Trujillo, Dominic Furniss, Jagdeep Nanchahal
Summary: Fibrosis, characterized by excessive accumulation of matrix protein, has significant impact on health in the Western world. However, there is a lack of effective antifibrotic treatments due to the difficulty in identifying targets for human fibrosis. In this study, researchers used Dupuytren's disease as a model to analyze the vasculature niche of human fibrosis at a single-cell resolution. The results showed distinct populations of endothelial and pericyte cells, and revealed a complex topological organization in the fibrotic microenvironment. It was found that endothelium promotes immune regulatory fibroblast phenotype through platelet-derived growth factor signaling, leading to an immune cell-enriched perivascular niche. Additionally, pericytes were found to house a putative myofibroblast precursor. These findings provide valuable insights for fibrosis research and highlight the therapeutic potential of targeting blood vessel signaling in human fibrosis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Ophthalmology
Yuanyuan Chen, Cheng Wu, Shanzhen Peng, Dianlei Guo, Hong Ouyang, Yanhong Wei, Rong Ju, Xiaoyan Ding, Zhi Xie, Chunqiao Liu
Summary: This study characterized the cell composition and molecular features of PFV using immunohistochemistry and single-cell RNA sequencing. They identified 10 defined cell types and analyzed their molecular features and functions, providing a foundation for further understanding the pathogenesis of PFV.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Review
Neurosciences
Jessica C. Barron, Emily P. Hurley, Matthew P. Parsons
Summary: Huntington disease is a monogenic disorder characterized by motor, psychiatric, and cognitive symptoms. While there is currently no cure, RNA-targeting therapies are being developed to reduce the production of mutant proteins. However, these therapies may inadvertently lower levels of non-pathogenic proteins, potentially leading to synaptic dysfunction.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Neurosciences
Magda Luciana de Paula Rosa, Caroline Amaral Machado, Bruna da Silva Oliveira, Eliana Cristina de Brito Toscano, Laila Asth, Joao Luis Vieira Monteiro de Barros, Antonio Lucio Teixeira, Fabricio A. Moreira, Aline Silva de Miranda
Summary: The study aimed to evaluate the levels of inflammatory mediators and neurotrophic factors in key areas of the central nervous system of mice subject to nicotine-induced CPP. Nicotine induced place preference behavior and resulted in increased peripheral levels of IL-6 and IL-10 alongside increased hippocampal levels of NGF but decreased GDNF in mice. In the striatum, nicotine promoted a decrease in IL-1ss, IL-10 and GDNF levels.
NEUROSCIENCE LETTERS
(2021)
Article
Cell Biology
Zhi-Han Zhu, Feng Jia, Waqas Ahmed, Gui-Long Zhang, Hong Wang, Chao-Qun Lin, Wang-Hao Chen, Lu-Kui Chen
Summary: In this study, we engineered exosomes (BDNF-hNSC-Exo) by loading brain-derived neurotrophic factor (BDNF) into exosomes derived from neural stem cells (NSCs). These engineered exosomes showed enhanced cell survival and promoted neuronal differentiation, suggesting their potential therapeutic role in ischemic stroke.
NEURAL REGENERATION RESEARCH
(2023)
Article
Neurosciences
Fanny L. Lemarie, Nicholas S. Caron, Shaun S. Sanders, Mandi E. Schmidt, Yen T. N. Nguyen, Seunghyun Ko, Xiaohong Xu, Mahmoud A. Pouladi, Dale D. O. Martin, Michael R. Hayden
Summary: Research has shown that palmitoylation of mHTT and HIP14/HIP14L substrates is decreased early in Huntington's disease models, further decreasing with aging. Palmitoylation of mHTT can be normalized using an APT inhibitor, reducing mHTT aggregation and cytotoxicity.
NEUROBIOLOGY OF DISEASE
(2021)
Review
Cell Biology
Austin Folger, Yanchang Wang
Summary: Protein misfolding and aggregation play a crucial role in neurodegenerative diseases, including Huntington's, where polyglutamine expansions lead to protein aggregation. Cells employ the ubiquitin-proteasome system and autophagy pathways to degrade misfolded proteins, emphasizing the importance of efficient protein degradation for cell health.
Article
Immunology
Khadeja-Tul Kubra, Mohammad A. Uddin, Mohammad S. Akhter, Antoinette J. Leo, Agnieszka Siejka, Nektarios Barabutis
Summary: The study shows that metformin can counteract LPS-induced lung microvascular dysfunction by inhibiting the formation of actin stress fibers and deactivating cofilin. Additionally, P53 inhibition increases paracellular permeability, which metformin is able to prevent.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Neurosciences
Debashis Dutta, Moumita Majumder, Ramesh Kumar Paidi, Kalipada Pahan
Summary: Huntington's disease is a neurodegenerative disorder characterized by mutant huntingtin protein accumulation and neuronal loss. This study found that the food flavoring ingredient glyceryl tribenzoate and the drug sodium benzoate can alleviate HD pathology, increase neuronal integrity, suppress glial activation and inflammation, and improve motor performance in HD mice. These results suggest that these compounds may be repurposed for HD treatment.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Cell & Tissue Engineering
Hyun Jung Park, Areum Han, Ji Yeon Kim, Jiwoo Choi, Hee Sook Bae, Gyu-Bon Cho, Hyejung Shin, Eun Ji Shin, Kang-In Lee, Seokjoong Kim, Jae Young Lee, Jihwan Song
Summary: Research has shown that editing the SUPT4H1 gene can reduce the expression of mutant HTT, thereby improving the symptoms of Huntington's disease. This study suggests that gene editing could be a strategy for treating Huntington's disease.
NPJ REGENERATIVE MEDICINE
(2022)
Article
Genetics & Heredity
Jin Xing, Li Ren, Hao Xu, Liang Zhao, Zhi-Han Wang, Guang-Dong Hu, Zi-Long Wei
Summary: This study reanalyzed a single-cell RNA sequencing dataset to identify key cellular and transcriptional changes associated with traumatic brain injury (TBI). The findings suggest that astrocytes and microglia play important roles in inflammation after TBI, and excitatory neurons may excessively transport and excrete glutamate in response to TBI. Additionally, a TBI-specific ependymal subpopulation was identified, and candesartan treatment was found to promote neuronal recovery post-TBI through neuroactive ligand-receptor interactions and reducing excitotoxicity.
FRONTIERS IN GENETICS
(2022)
Article
Chemistry, Multidisciplinary
Caijuan Li, Yingqi Lin, Yizhi Chen, Xichen Song, Xiao Zheng, Jiawei Li, Jun He, Xiusheng Chen, Chunhui Huang, Wei Wang, Jianhao Wu, Jiaxi Wu, Jiale Gao, Zhuchi Tu, Xiao-Jiang Li, Sen Yan, Shihua Li
Summary: Researchers designed a peptide that specifically binds mutant huntingtin and its aggregates, and brings them into lysosomes for degradation, thereby improving neuropathology and behavioral abnormalities in HD KI-140Q mice.
Article
Neurosciences
Dinesh C. Joshi, Chuan-Li Zhang, Deepali Mathur, Alex Li, Gaurav Kaushik, Zu-Hang Sheng, Shing-Yan Chiu
Summary: The interaction between pro-inflammatory cytokine IL-1/I and NMDA triggers the misplacement of mitochondrial anchor protein SNPH into neuronal dendrites, leading to excitotoxicity. Blocking the interaction between IL-1/I and NMDAR can prevent the intrusion of SNPH into dendrites. Neuronal toxicity caused by IL-1/I or NMDA is significantly reduced in SNPH-/- neurons. Targeting dendritic SNPH in the tripartite IL-1/I/NMDAR/SNPH interaction could be a strategic approach to ameliorate neurotoxicity in inflammatory diseases.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Marie Rieux, Melanie Alpaugh, Giacomo Sciacca, Martine Saint-Pierre, Maria Masnata, Helena L. Denis, Sebastien A. Levesque, Frank Herrmann, Chantal Bazenet, Alexandre P. Garneau, Paul Isenring, Ray Truant, Abid Oueslati, Peter Gould, Anne Ast, Erich E. Wanker, Steve Lacroix, Francesca Cicchetti
Summary: Huntington's disease is a monogenic neurodegenerative disorder caused by a mutation in the huntingtin gene, with evidence suggesting that the mutant huntingtin protein (mHTT) can spread through the bloodstream and induce pathology. Through a parabiosis approach, it was observed that mHTT can propagate and cause pathological changes in normal mice, while healthy blood can attenuate pathology. These findings have implications for the development of therapies for HD.
MOLECULAR PSYCHIATRY
(2021)
Article
Clinical Neurology
Adham Fani Maleki, Giulia Cisbani, Nataly Laflamme, Paul Prefontaine, Marie-Michele Plante, Joanie Baillargeon, Manu Rangachari, Jean Gosselin, Serge Rivest
Summary: Muramyl dipeptide (MDP) activates the NOD2 receptor and demonstrates selective immunomodulatory and therapeutic effects in mouse models of multiple sclerosis (MS), delaying disease onset and reducing infiltration of leukocytes into the CNS. The NOD2 receptor plays a critical role in MDP-mediated resistance to experimental autoimmune encephalomyelitis (EAE), indicating the potential for developing NOD2 agonist-based medications for MS in the future.
Article
Biochemistry & Molecular Biology
Giulia Cisbani, Richard P. Bazinet
Summary: This review synthesizes the current knowledge on circulating fatty acids as biomarkers for Alzheimer's disease (AD). While some fatty acids appear to be modulated during disease progression, discrepant results have been reported in the literature, indicating the need for further validation and method standardization. However, fatty acid analyses have the potential to provide valuable data to inform the pathology and progression of AD.
PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
(2021)
Article
Behavioral Sciences
Giulia Cisbani, Silvia Poggini, Nataly Laflamme, Vincent Pons, Marie-Eve Tremblay, Igor Branchi, Serge Rivest
Summary: The study aimed to phenotype the behavior of cuprizone-fed mice using the automated system Intellicage. The results consistently showed reduced activity and impulsivity in cuprizone-fed mice. This suggests that behavioral phenotyping using Intellicage is reproducible and sensitive in detecting changes missed by standard behavioral tests.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Endocrinology & Metabolism
Evan J. H. Lewis, Leif E. Lovblom, Giulia Cisbani, Daniel K. Chen, Richard P. Bazinet, Thomas M. S. Wolever, Bruce A. Perkins, Vera Bril
Summary: This study found an association between low plasma DHA and prevalent DSP in patients with T1D, while n-3 therapy increased blood n-3 levels and promoted nerve regeneration, with higher baseline n-3 levels correlating with greater nerve regeneration.
JOURNAL OF DIABETES AND ITS COMPLICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Giulia Cisbani, Serge Rivest
Summary: Innate immunity plays a crucial role in understanding the pathogenesis of brain diseases, especially Alzheimer's disease. Initially thought to be a key target for treating brain diseases, recent studies have shown that innate immune cells may actually have beneficial properties and could be targeted for neuroprotection.
MOLECULAR PSYCHIATRY
(2021)
Review
Nutrition & Dietetics
Mackenzie E. Smith, Giulia Cisbani, R. J. Scott Lacombe, Richard P. Bazinet
Summary: This scoping review aimed to explore the effects of PO/POL and SN2 on neurodevelopment in infants, revealing a lack of consistent findings in this area. Current research indicates that feeding formulas containing PO/POL or SN2 does not significantly impact physical growth, but may affect the absorption of nutrients differently.
JOURNAL OF NUTRITION
(2021)
Article
Biochemistry & Molecular Biology
Mackenzie E. Smith, Giulia Cisbani, Adam H. Metherel, Richard P. Bazinet
Summary: The study revealed that de novo lipogenesis from dietary sugars is a compensatory mechanism to maintain brain palmitic acid, especially under low PAM diet conditions. Additionally, there were differences in the ability to regulate DNL in the liver and brain based on sex, while anxiety-like behaviors were correlated with markers of LP diet consumption.
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Giulia Cisbani, Alex Koppel, Adam H. Metherel, Mackenzie E. Smith, Kankana N. Aji, Ana C. Andreazza, Romina Mizrahi, Richard P. Bazinet
Summary: Cannabis use is associated with increased fatty acid metabolism, as indicated by higher levels of saturated and monounsaturated fatty acids in the serum of cannabis users compared to nonusers. The elevated lipogenic activity in cannabis users may be influenced by the endocannabinoid 2-arachidonoylglycerol, which could activate the cannabinoid receptor 1. However, further studies are needed to confirm these findings and control for dietary intake.
Review
Biochemistry & Molecular Biology
Melanie Alpaugh, Helena L. Denis, Francesca Cicchetti
Summary: Current research accepts the theory that pathological proteins associated with neurodegenerative disorders behave similarly to prions. Protein misfolding and prion-like properties play significant roles in neurodegenerative disorders, influencing disease progression and potential therapeutic strategies.
MOLECULAR PSYCHIATRY
(2022)
Article
Biotechnology & Applied Microbiology
Melanie Alpaugh, Maria Masnata, Aurelie de Rus Jacquet, Eva Lepinay, Helena L. Denis, Martine Saint-Pierre, Peter Davies, Emmanuel Planel, Francesca Cicchetti
Summary: This study suggests that attenuating tau pathology could mitigate behavioral and molecular hallmarks associated with Huntington's disease.
Article
Biochemistry & Molecular Biology
Giulia Cisbani, Adam H. Metherel, Mackenzie E. Smith, Richard P. Bazinet
Summary: The study characterized the fatty acid composition of murine microglia cells from young male and female mice, as well as human microglia cells, finding that EPA was relatively abundant in microglia cells compared to DHA. Furthermore, the study discovered that the DHA to EPA ratio was about 400 times higher in microglial cells compared to a myelin-enriched fraction from the same mice.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Editorial Material
Neurosciences
Aurelie de Rus Jacquet, Francesca Cicchetti
Summary: The study highlights the potential of in situ brain regeneration as a non-pharmacological approach to treat neurodegeneration in the epileptic brain, offering a new direction for the treatment of drug-refractory neurological diseases.
MOLECULAR NEURODEGENERATION
(2022)
Article
Biochemistry & Molecular Biology
Morgan Berard, Razan Sheta, Sarah Malvaut, Raquel Rodriguez-Aller, Maxime Teixeira, Walid Idi, Roxanne Turmel, Melanie Alpaugh, Marilyn Dubois, Manel Dahmene, Charleen Sales, Jerome Lamontagne-Proulx, Marie-Kim St-Pierre, Omid Tavassoly, Wen M. Luo, Esther Del Cid-Pellitero, Raza Qazi, Jae-Woong Jeong, Thomas Durcan, Luc Vallieres, Marie-Eve A. Tremblay, Denis Soulet, Martin Levesque, Francesca Cicchetti, Edward Fon, Armen Saghatelyan, Abid Oueslati
Summary: Neurodegenerative disorders are associated with abnormal protein accumulation and aggregation in the central nervous system. This study developed a light-inducible protein aggregation system that allows for the control and investigation of alpha-synuclein aggregation in Parkinson disease. The findings demonstrate that this system mimics key features of authentic Lewy bodies and induces neurodegeneration and motor impairments in vivo.
Review
Biochemistry & Molecular Biology
Eva Lepinay, Francesca Cicchetti
Summary: Developing effective treatments for Huntington's disease is challenging, and finding robust biomarkers is crucial for diagnosis and treatment.
MOLECULAR PSYCHIATRY
(2023)