Review
Biochemistry & Molecular Biology
Sydney Brockie, James Hong, Michael G. Fehlings
Summary: Neuroinflammation plays a crucial role in the development of spinal cord injury, with microglia being key players in modulating the inflammatory response. Microglia interact with different cell types to facilitate injury response, but further research is needed to fully understand their mechanisms of action and spatial and temporal profiles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Yue Guo, Peng Zhang, Haosen Zhao, Chang Xu, Sen Lin, Xifan Mei, He Tian
Summary: In this study, melatonin was found to promote the beneficial polarization of microglia from pro-inflammatory to anti-inflammation, decrease ROS activity, and restore mitochondrial metabolism. Melatonin may have therapeutic potential for neuroinflammation-related neurological disorders, such as spinal cord injury.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Neurosciences
Meng-Tong Xue, Wen-Jie Sheng, Xue Song, Yu-Jiao Shi, Zhi-Jun Geng, Lin Shen, Rui Wang, He-Zuo Lu, Jian-Guo Hu
Summary: ATL-III improves spinal cord injury by modulating microglial/macrophage polarization, and it possesses anti-inflammatory and neuroprotective effects.
CNS NEUROSCIENCE & THERAPEUTICS
(2022)
Review
Immunology
Qi-Ming Pang, Si-Yu Chen, Qi-Jing Xu, Meng Zhang, Da-Fei Liang, Sheng-Ping Fu, Jiang Yu, Zu-Lin Liu, Qian Zhang, Tao Zhang
Summary: This study reviews the effects of neuroinflammation on SCI, with a focus on the contributions and interactions of microglia and astrocytes. It also discusses therapeutic strategies to regulate their immunophenotype in order to suppress inflammation and improve injury prognosis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Carlota Jauregui, Idoia Blanco-Luquin, Monica Macias, Miren Roldan, Cristina Caballero, Inma Pagola, Maite Mendioroz, Ivonne Jerico
Summary: This study investigates the expression patterns of microglial-related genes in ALS spinal cord, and suggests the presence of a DAM-mediated inflammatory response and the significant role of TREM2 in the immune function of microglia in ALS.
Article
Medicine, Research & Experimental
Yun Li, Zhuofan Lei, Rodney M. Ritzel, Junyun He, Hui Li, Harry M. C. Choi, Marta M. Lipinski, Junfang Wu
Summary: Autophagy plays a crucial role in post-spinal cord injury, as inhibiting autophagy can lead to pro-inflammatory activation in microglia and worse functional outcomes, while increasing autophagy can reduce inflammation and improve outcomes.
Review
Clinical Neurology
Lintao Xu, Jingyu Wang, Yueming Ding, Linlin Wang, Yong-Jian Zhu
Summary: Microglia undergo activation, proliferation, and changes in gene and protein expression and morphology after traumatic spinal cord injury (SCI), leading to both detrimental and beneficial effects. Understanding and regulating microglial activation status is crucial for reducing harmful effects, promoting repair, and developing effective therapies for SCI.
FRONTIERS IN NEUROLOGY
(2022)
Article
Engineering, Biomedical
Ciara M. Walsh, Jacek K. Wychowaniec, Louise Costello, Dermot F. Brougham, Dearbhaile Dooley
Summary: Spinal cord injury (SCI) is a devastating condition without effective treatment options. Immunomodulation, using locally injected hydrogels carrying immunotherapeutic cargo, shows promise as a potential therapeutic strategy for SCI. Gelatin methacrylate (GelMA) hydrogels are a promising candidate, but their immunogenicity in the SCI microenvironment has not been fully studied yet. This study analyzes the immunogenicity of GelMA hydrogels formulated with a relevant photoinitiator, both in vitro and ex vivo.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Neurosciences
Rui Liu, Ying Li, Ziyue Wang, Peng Chen, Yi Xie, Wensheng Qu, Minghuan Wang, Zhiyuan Yu, Xiang Luo
Summary: After spinal cord injury (SCI), immune cells and proinflammatory cytokines infiltrate the spinal cord and disrupt the microenvironment, hindering axon regeneration and functional recovery. Previous studies have shown that regulatory T cells (Tregs) can enter the central nervous system and suppress microglia during conditions like multiple sclerosis and stroke. However, the interaction between Tregs and microglia and their role in modulating the injured microenvironment after SCI remains unknown.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Multidisciplinary Sciences
Lauren Mifflin, Zhirui Hu, Connor Dufort, Cynthia C. Hession, Alec J. Walker, Kongyan Niu, Hong Zhu, Nan Liu, Jun S. Liu, Joshua Z. Levin, Beth Stevens, Junying Yuan, Chengyu Zou
Summary: The study identifies a subclass of microglia, termed RIPK1-Regulated Inflammatory Microglia (RRIMs), in mouse models of ALS. RRIMs show significant up-regulation of proinflammatory pathways, are highly regulated by TNF alpha signaling, and their prevalence can be suppressed by inhibiting RIPK1 activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Immunology
Xue Wu, Yaping Yan, Qian Zhang
Summary: This study focuses on the pathogenesis of neuroinflammation after spinal cord injury and the effects of natural compounds. By analyzing the impact of natural products on neuroinflammation, it provides important insights for further research and drug development.
JOURNAL OF INFLAMMATION RESEARCH
(2021)
Article
Neurosciences
Kyle J. Trageser, Eun-Jeong Yang, Chad Smith, Ruth Iban-Arias, Tatsunori Oguchi, Maria Sebastian-Valverde, Umar Haris Iqbal, Henry Wu, Molly Estill, Md Al Rahim, Urdhva Raval, Francis J. Herman, Yong Jie Zhang, Leonard Petrucelli, Giulio Maria Pasinetti
Summary: Hexanucleotide repeat expansions in C9orf72 gene cause frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) and lead to the production of toxic dipeptide repeat (DPR) proteins, with poly(glycine-arginine) (GR) being the most toxic and accumulating in relevant brain regions. Neuroinflammation is a driving factor in the disease, and increased inflammasome-mediated neuroinflammation is observed in C9orf72 FTD/ALS mice, suggesting a role for HRE in innate immunity and the NLRP3 inflammasome as a potential therapeutic target.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Clinical Neurology
Ruideng Wang, Rubing Zhou, Zhengyang Chen, Shan Gao, Fang Zhou
Summary: Glial cells play crucial roles in the healthy functioning of the central nervous system and in the repair of spinal cord injuries.
FRONTIERS IN NEUROLOGY
(2022)
Article
Immunology
Xin-Qiang Yao, Jia-Ying Chen, Zi-Han Yu, Zu-Cheng Huang, Regan Hamel, Yong-Qiang Zeng, Zhi-Ping Huang, Ke-Wu Tu, Jun-Hao Liu, Yan-Meng Lu, Zhi-Tao Zhou, Stefano Pluchino, Qing-An Zhu, Jian-Ting Chen
Summary: The study identified APOE as a crucial hub gene in macrophages and microglia following spinal cord injury, playing a key role in neuroinflammation and recovery. Knocking out APOE exacerbated neurological dysfunction, increased neuroinflammation, and worsened white matter loss.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Neurosciences
Xvlei Hu, Yifan Zhang, Lei Wang, Jiangwei Ding, Mei Li, Hailiang Li, Liang Wu, Zhong Zeng, Hechun Xia
Summary: This study found that microglia activation in the primary motor cortex (M1) after spinal cord injury (SCI) mediates chronic neuroinflammation and neuronal damage. The use of minocycline, a microglia inhibitor, can reduce inflammation-induced neuronal damage, protect the integrity of the motor conduction pathway, and promote motor function recovery.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Clinical Neurology
Jane E. Alty, Aidan D. Bindoff, Kimberley E. Stuart, Eddy Roccati, Jessica M. Collins, Anna E. King, Mathew J. Summers, James C. Vickers
Summary: Females have a higher incidence of Alzheimer's disease than males, but the reasons for this are unclear. One possible factor is that females historically had less access to education and may have accumulated less cognitive reserve. However, educational attainment is confounded by IQ, which does not differ between sexes and is a component of cognitive reserve.
Review
Biochemistry & Molecular Biology
David Stellon, Jana Talbot, Alex W. W. Hewitt, Anna E. E. King, Anthony L. L. Cook
Summary: Neurodegenerative diseases lead to progressive loss of neuronal structure and function, causing cell death and irreversible brain atrophy. While the mechanisms of neurodegeneration are still unknown, genetically encodable fluorescent biosensors (GEFBs) offer a unique way to study disease mechanisms and identify new therapies when combined with induced pluripotent stem cells (iPSCs).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Geriatrics & Gerontology
Fariha Kabir, Rachel Atkinson, Anthony L. Cook, Andrew James Phipps, Anna Elizabeth King
Summary: Acetylation is an important post-translational modification involved in cellular regulation and is crucial for memory and learning. Imbalances in acetylation have been found in neurodegenerative diseases, such as AD, PD, HD, and ALS, and can lead to the accumulation of pathophysiological proteins. The dysregulation of acetylation is also associated with impaired axonal transport in ALS, a key pathological mechanism.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Medicine, General & Internal
Jing Tian, Graeme Jones, Xin Lin, Yuan Zhou, Anna King, James Vickers, Feng Pan
Summary: This study investigates the association between the number of chronic pain sites and the risk of dementia and its subtypes. The findings suggest that a greater number of chronic pain sites is associated with an increased risk of all-cause dementia and Alzheimer's disease, but not vascular and frontotemporal dementia.
Article
Neurosciences
Gary P. P. Morris, Catherine G. G. Foster, Jo-Maree Courtney, Jessica M. M. Collins, Jake M. M. Cashion, Lachlan S. S. Brown, David W. W. Howells, Gabriele C. C. DeLuca, Alison J. J. Canty, Anna E. E. King, Jenna M. M. Ziebell, Brad A. A. Sutherland
Summary: We discovered a subset of microglia, called pericyte-associated microglia (PEM), that closely associate with pericytes. PEM are present in the brain and spinal cord, and their number is reduced in the superior frontal cortex in Alzheimer's disease (AD). This may contribute to vascular dysfunction in neurodegenerative diseases.
Article
Biochemistry & Molecular Biology
Jennilee M. Davidson, Stephanie L. Rayner, Sidong Liu, Flora Cheng, Antonio Di Ieva, Roger S. Chung, Albert Lee
Summary: Proteomics has great potential in studying the molecular regulation of the human brain. This study compared the efficiency of two different protein-extraction buffers on formalin-fixed human brains, and found that a lysis buffer containing TrisHCl, SDS, SDC, and Triton X-100 had superior protein extraction performance. The analysis also revealed differential enrichment of proteins in different brain regions, indicating commonalities in the molecular regulation of neuroanatomically-linked brain functions. Overall, the study developed an optimized method for protein extraction from formalin-fixed human brain tissue and demonstrated its suitability for rapid and routine analysis of molecular signaling pathways in the human brain.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Rowan A. W. Radford, Stephanie L. Rayner, Paulina Szwaja, Marco Morsch, Flora Cheng, Tianyi Zhu, Jocelyn Widagdo, Victor Anggono, Dean L. Pountney, Roger Chung, Albert Lee
Summary: Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by the presence of insoluble phosphorylated-Tau (p-Tau) in neurons and glia. In this study, a proteomic approach using antibody-mediated biotinylation and mass spectrometry (MS) was used to identify proteins near p-Tau inclusions in PSP. The results showed the presence of previously identified interacting proteins of Tau and known modifiers of Tau aggregation, as well as 19 novel proteins associated with Tau. Additionally, the study found proteins related to neurological disorders and pathways involved in various cellular processes.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Chemistry, Medicinal
Jessica Merjane, Roger Chung, Rickie Patani, Leszek Lisowski
Summary: Despite the mysterious etiology, differentiated treatments are required for ALS to address both familial and sporadic cases. Targeting mechanisms of defective protein homeostasis and RNA processing, as well as exploring the use of gene therapy through adeno-associated virus (AAV) for gene delivery to the CNS, might provide potential therapeutic interventions. Overall, there is a strong need for disease modifying treatments for ALS that can effectively treat the full spectrum of cases.
MEDICINAL RESEARCH REVIEWS
(2023)
Article
Neurosciences
Jennilee M. Davidson, Sharlynn S. L. Wu, Stephanie L. Rayner, Flora Cheng, Kimberley Duncan, Carlo Russo, Michelle Newbery, Kunjie Ding, Natalie M. Scherer, Rachelle Balez, Alberto Garcia-Redondo, Alberto Rabano, Livia Rosa-Fernandes, Lezanne Ooi, Kelly L. Williams, Marco Morsch, Ian P. Blair, Antonio Di Ieva, Shu Yang, Roger S. Chung, Albert Lee
Summary: This study reveals the role of cyclin F in regulating substrate solubility and its contribution to the pathogenesis of ALS and FTD. The ALS and FTD-associated protein p62 is identified as a substrate of cyclin F, and its aggregation is promoted by cyclin F expression. Mutations in cyclin F result in dysregulated p62 solubility and formation of p62 foci, which are associated with ALS and FTD pathogenesis.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Clinical Neurology
Annika van Hummel, Miheer Sabale, Magdalena Przybyla, Julia van der Hoven, Gabriella Chan, Astrid F. Feiten, Roger S. Chung, Lars M. Ittner, Yazi D. Ke
Summary: This study developed the first mouse models expressing wild-type and mutant human CCNF genes to replicate the key clinical and neuropathological features of ALS and FTD linked to CCNF disease variants. The results showed that these mice exhibited behavioral abnormalities similar to FTD patients, as well as memory deficits. Furthermore, the study found altered CCNF-mediated pathways and abnormal TDP-43 neuropathology, which are key hallmarks of FTD/ALS pathology.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Public, Environmental & Occupational Health
Larissa Bartlett, Aidan Bindoff, Kathleen Doherty, Sarang Kim, Claire Eccleston, Alex Kitsos, Eddy Roccati, Jane Alty, Anna E. King, James C. Vickers
Summary: The ISLAND study utilizes personalized DRP reports and a four-week PDMOOC to increase dementia risk knowledge and stimulate health behavior change for dementia risk reduction.
Article
Geriatrics & Gerontology
Eddy Roccati, Jessica Marie Collins, Aidan David Bindoff, Jane Elizabeth Alty, Larissa Bartlett, Anna Elizabeth King, James Clement Vickers
Summary: This study examined the associations between modifiable dementia risk factors, cognition, and plasma phosphorylated p-tau 181. The results showed that lower education was associated with lower cognitive scores, but modifiable dementia risk factors were not associated with plasma p-tau 181. Nonmodifiable factors such as age, education, sex, and apolipoprotein E epsilon 4 displayed significant associations with cognition and plasma p-tau 181. This study contributes to the understanding of confounding factors in the interpretation of blood-based biomarkers for dementia.
NEUROBIOLOGY OF AGING
(2023)
Article
Neurosciences
Jessica M. Collins, Aidan D. Bindoff, Eddy Roccati, Jane E. Alty, James C. Vickers, Anna E. King
Summary: This study examined the relationship between serum NfL levels and cognition in unimpaired older adults, and found that higher serum NfL levels were positively associated with age, while cognitive test scores were negatively associated with age. However, serum NfL levels did not mediate the relationship between age and cognitive test scores.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Cell Biology
Afshin Babazadeh, Stephanie L. Rayner, Albert Lee, Roger S. Chung
Summary: A common feature of adult-onset neurodegenerative diseases is the presence of specific pathological protein accumulations. Restoring protein homeostasis of these accumulations may represent a potential therapeutic strategy. This review discusses the mechanisms leading to disrupted protein homeostasis and explores small molecule-based therapies for modulating these mechanisms.
AGEING RESEARCH REVIEWS
(2023)
Letter
Clinical Neurology
J. Tian, G. Jones, X. Lin, Y. Zhou, A. King, J. Vickers, Feng Pan
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2023)