Review
Biochemistry & Molecular Biology
Ines Ramos Rego, Beatriz Santos Cruz, Antonio Francisco Ambrosio, Celso Henrique Alves
Summary: TRAP1, a mitochondrial molecular chaperone, plays important roles in protein folding and maintaining mitochondrial integrity. It is involved in cellular metabolism, redox homeostasis, oxidative stress, and apoptosis. While extensively studied in oncology, its role in central nervous system cells remains unclear.
Review
Biochemistry & Molecular Biology
Ricardo Pardillo-Diaz, Patricia Perez-Garcia, Carmen Castro, Pedro Nunez-Abades, Livia Carrascal
Summary: Neurodegenerative diseases are characterized by selective loss of neuronal systems and can be influenced by oxidative stress, inflammation, and increased neuronal excitability.
Article
Biochemistry & Molecular Biology
Carlos Vicente-Gutierrez, Daniel Jimenez-Blasco, Ruben Quintana-Cabrera
Summary: Metabolism and redox signalling are closely interconnected in the nervous system, with ROS playing a crucial role in their communication. Neurons and astrocytes exhibit different mechanisms for ROS production and handling, but both are tightly regulated.
NEUROCHEMICAL RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Francesco D'Egidio, Vanessa Castelli, Annamaria Cimini, Michele d'Angelo
Summary: Huntington's Disease (HD) is a hereditary neurodegenerative disorder caused by the expansion of a CAG triplet repeat in the HTT gene, resulting in the production of an aberrant huntingtin (Htt) protein. The accumulation of mutant protein leads to neuronal dysfunction and cell death, primarily through oxidative damage, excitotoxicity, inflammation, and mitochondrial impairment. This review aims to provide an overview of the cell's response to stress in HD, with a focus on the role of oxidative stress and its interaction with the antioxidant system.
Editorial Material
Cell Biology
Shree Padma Metur, Daniel J. Klionsky
Summary: Maintaining mitochondrial quality control is crucial for neuronal homeostasis, and dysregulation of this process has been implicated in neurodegenerative diseases. This study demonstrates that neurons sustain axonal mitophagy by locally translating Pink1 mRNA that is co-transported with mitochondria to the distal axons, providing a continuous supply of PINK1 protein.
Article
Marine & Freshwater Biology
Jiangfei Chen, Aijun Kong, Delia Shelton, Haojia Dong, Jiani Li, Fan Zhao, Chenglian Bai, Kaiyu Huang, Wen Mo, Shan Chen, Hui Xu, Robyn L. Tanguay, Qiaoxiang Dong
Summary: Aristolochic acids (AA) are nitrophenanthrene carboxylic acids found in plants of the Aristolochiaceae family. Exposure to AA can result in developmental neurotoxicity in zebrafish, characterized by larval hyperactivity and changes in motor neuron proliferation, eye apoptosis, oxidative stress, and vision gene expression. The most sensitive exposure window for AA-induced hyperactivity is identified as 8-24 hours post fertilization.
AQUATIC TOXICOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Eleonora Zilio, Valentina Piano, Brunhilde Wirth
Summary: This review discusses the impact of spinal muscular atrophy (SMA) on mitochondrial functions in the neuronal and muscular systems, highlighting the potential contribution of mitochondrial defects to disease progression and the potential of restoring mitochondrial functionality as a therapeutic approach. The study also provides a list of transcripts encoding mitochondrial proteins affected in various SMA models and speculates that age-related mitochondrial deterioration may play a crucial role in adult SMA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Ines Ramos Rego, Daniela Silverio, Maria Isabel Eufrasio, Sandra Sofia Pinhancos, Bruna Lopes da Costa, Jose Teixeira, Hugo Fernandes, Yang Kong, Yao Li, Stephen H. Tsang, Paulo J. Oliveira, Rosa Fernandes, Peter M. J. Quinn, Paulo Fernando Santos, Antonio Francisco Ambrosio, Celso Henrique Alves
Summary: Age-related macular degeneration (AMD) is a major cause of visual impairment and blindness in the elderly. The damage to retinal pigment epithelium (RPE) caused by oxidative stress is a key factor in the development of AMD, and this damage is caused by the accumulation of reactive oxygen species (ROS) primarily produced by mitochondria. The protein TRAP1, found in mitochondria, helps maintain mitochondrial integrity and reduces ROS production. This study found that TRAP1 is present in human RPE cells and its levels decrease when exposed to hydrogen peroxide. Silencing TRAP1 leads to increased ROS production and decreased mitochondrial respiratory capacity in RPE cells.
Article
Biochemistry & Molecular Biology
Ning Wang, Hai Yu, Qian Song, Ping Mao, Kuo Li, Gang Bao
Summary: The study developed and characterized SM@SA-CS nanomicelles, showing potential therapeutic effects in oxidative stress in neural cells.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Review
Biochemistry & Molecular Biology
Laura A. Wengert, Sarah J. Backe, Dimitra Bourboulia, Mehdi Mollapour, Mark R. Woodford
Summary: Mitochondrial function relies on molecular chaperones, including heat shock proteins (Hsps) such as Hsp90 and its chaperone TNF-receptor-associated protein-1 (TRAP1). TRAP1, primarily localized in mitochondria, plays a crucial role in cellular metabolic reprogramming and mitochondrial apoptosis. Upregulation of TRAP1 promotes the growth of cancer cells by enhancing glycolytic metabolism and inhibiting mitochondrial permeability transition, while attenuation of TRAP1 induces apoptosis in cancer cells. Furthermore, TRAP1 is subject to post-translational modifications that regulate its function and downstream effectors.
Article
Biochemistry & Molecular Biology
Jonas Knittel, Nadja Itani, Rolf Schreckenberg, Jacqueline Heger, Susanne Rohrbach, Rainer Schulz, Klaus-Dieter Schlueter
Summary: Serotonin effects on cardiac hypertrophy, senescence, and failure depend on specific receptors or serotonin uptake and degradation by MAOs. MAO-dependent effects are non-specific. MAOA expression increases in maladaptive hypertrophic stages. MAO-A inhibition suppresses serotonin-dependent damage. Serotonin induces mitochondria-dependent oxidative stress.
Review
Cell Biology
Cassandra Barone, Xin Qi
Summary: Motor Neuron Diseases (MND) are neurological disorders characterized by a loss of motor neurons resulting in decreased physical capabilities. Current research aims to hinder disease progression by understanding the causes of motor neuron death, particularly focusing on metabolic malfunction as a potential therapeutic target. This review highlights the importance of a cohesive system involving both neurons and skeletal muscle tissue and proposes potential metabolic deficits as targets for future intervention.
Article
Biochemistry & Molecular Biology
Lingxiao Zhang, Yuanyuan Luo, Linyan Lv, Siyong Chen, Guihua Liu, Tongfeng Zhao
Summary: Mitochondrial dysfunction and cell apoptosis are prominent features in primary cardiomyocytes under high glucose/palmitate conditions. MIC60, a core component of mitochondrial cristae, is decreased via ubiquitination and degradation. MARCH5 acts as an E3 ubiquitin ligase that targets MIC60, leading to its degradation and the induction of mitochondrial dysfunction and apoptosis. TRAP1 competes with MARCH5 for binding to MIC60, inhibiting its ubiquitination.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Neurosciences
Asako Onda-Ohto, Minami Hasegawa-Ogawa, Hiromasa Matsuno, Tomotaka Shiraishi, Keiko Bono, Hiromi Hiraki, Yumi Kanegae, Yasuyuki Iguchi, Hirotaka James Okano
Summary: This study introduced TDP-43 mutations into healthy human iPSCs, differentiated them into motor and sensory neurons, and analyzed factors associated with ALS. The results showed that motor neurons with TDP-43 mutation were more vulnerable to oxidative stress, which is crucial for understanding the pathogenesis of ALS and developing treatments for the disease.
Article
Biochemistry & Molecular Biology
Rafael Lopez-Blanch, Rosario Salvador-Palmer, Jose M. Estrela, Elena Obrador
Summary: Oxidative stress is proposed as a major mechanism of motor neuron damage in the progression of ALS. The reactive phenotype of astrocytes may both protect neurons and contribute to oxidative stress that can harm motor neurons. Increased proinflammatory interleukin 6 levels in ALS may facilitate GSH release from the liver to blood circulation, providing antioxidant protection to motor neurons.
Article
Cell Biology
Benjamin E. Clarke, Rebecca San Gil, Jing Yip, Bernadett Kalmar, Linda Greensmith
CELL STRESS & CHAPERONES
(2019)
Review
Neurosciences
Benjamin E. Clarke, Doaa M. Taha, Giulia E. Tyzack, Rickie Patani
Summary: Increasing evidence suggests that astrocytes exhibit functional heterogeneity in different brain regions, with their diversity determining a spectrum of physiological states. They are now seen as viable targets for therapies aiming to restore neural circuit integrity in neurodegenerative disorders, and understanding their physiology and functional diversity will guide therapeutic strategies in these diseases.
Letter
Clinical Neurology
Benjamin E. Clarke, Doaa M. Taha, Oliver J. Ziff, Aftab Alam, Eric P. Thelin, Nuria Marco Garcia, Adel Helmy, Rickie Patani
Review
Clinical Neurology
Benjamin E. Clarke, Rickie Patani
Review
Neurosciences
Hannah Franklin, Benjamin E. Clarke, Rickie Patani
Summary: Astrocytes and microglia play critical roles in maintaining homeostasis and immune functions in the healthy central nervous system, with dysfunction implicated in various neurodegenerative diseases. Human in vitro models offer unique insights into disease biology by providing a manipulable model system directly from patients.
PROGRESS IN NEUROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Oliver J. Ziff, Doaa M. Taha, Hamish Crerar, Benjamin E. Clarke, Anob M. Chakrabarti, Gavin Kelly, Jacob Neeves, Giulia E. Tyzack, Nicholas M. Luscombe, Rickie Patani
Summary: This study reveals that decreased intron retention is common in astrocytes carrying ALS-causing mutations, and the overrepresented transcripts involved in reactive transformation are related to processes such as cell adhesion, stress response, and immune activation. The findings suggest a molecular model where poised nuclear reactivity-related IR transcripts are translocated and translated, providing new insights into the molecular regulation of reactive transformation in astrocytes.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Cell Biology
Rebecca San Gil, Benjamin E. Clarke, Heath Ecroyd, Bernadett Kalmar, Linda Greensmith
Summary: The study examined regional variations in the expression of Hsp25 in glia of the central nervous system, revealing that Hsp25 expression is not upregulated under acute or chronic stress conditions.
Review
Biochemistry & Molecular Biology
Jasmine Harley, Benjamin E. Clarke, Rickie Patani
Summary: RNA binding proteins play key roles in gene expression and their dysregulation has been implicated in the pathomechanisms of various neurodegenerative diseases, including ALS. Oxidative stress and mitochondrial dysfunction also play important roles in these diseases. The review highlights the mechanistic interplay between RNA binding protein dysregulation, oxidative stress, and mitochondrial dysfunction in ALS, and discusses potential therapeutic strategies targeting these pathways.
Article
Clinical Neurology
Doaa M. Taha, Benjamin E. Clarke, Claire E. Hall, Giulia E. Tyzack, Oliver J. Ziff, Linda Greensmith, Bernadett Kalmar, Mhoriam Ahmed, Aftab Alam, Eric P. Thelin, Nuria Marco Garcia, Adel Helmy, Christopher R. Sibley, Rickie Patani
Summary: This study investigates the cellular autonomy and uniformity of astrocyte reactive transformation in different genetic forms of amyotrophic lateral sclerosis. By using enriched and human induced pluripotent stem cell-derived astrocytes from patients with VCP and SOD1 mutations, the study shows that reactive transformation can occur cell-autonomously in ALS astrocytes and there is molecular and functional heterogeneity between different disease-causing mutations.
Article
Biochemistry & Molecular Biology
Oliver J. Ziff, Benjamin E. Clarke, Doaa M. Taha, Hamish Crerar, Nicholas M. Luscombe, Rickie Patani
Summary: This study reveals that astrocytes in amyotrophic lateral sclerosis (ALS) exhibit inflammatory reactive features and suppress neuronal support mechanisms. These findings offer potential therapeutic targets for ALS.
Review
Clinical Neurology
Phillip Smethurst, Hannah Franklin, Benjamin E. Clarke, Katie Sidle, Rickie Patani
Summary: Accumulating evidence suggests that astrocytes play a key role in neurodegenerative diseases by dealing with pathological protein aggregates and their prion-like behavior. However, their specific functions and their interactions with the disease process are still unclear.