Review
Cell Biology
Elena V. Mitroshina, Maria O. Savyuk, Evgeni Ponimaskin, Maria V. Vedunova
Summary: Hypoxia is a common pathological condition induced by various events, with the body's adaptation to it being crucial for health and disease. HIFs, a family of transcription factors, play a key role in cellular responses to hypoxia and are increasingly viewed as potential targets for treating a range of hypoxia-associated diseases. The role of HIFs in adaptation to hypoxia is universal across tissue types, including the CNS, where they are involved in regulating neurogenesis, nerve cell differentiation, and neuronal apoptosis, potentially offering new therapeutic opportunities.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Immunology
Qianyan He, Yinzhong Ma, Jie Liu, Dianhui Zhang, Jiaxin Ren, Ruoyu Zhao, JunLei Chang, Zhen-Ni Guo, Yi Yang
Summary: Ischemic stroke, caused by inadequate cerebrovascular blood and oxygen supply, poses a significant global health burden. HIF-1α, a key regulator of oxygen homeostasis, plays a critical role in various aspects of stroke pathophysiology and is an important target for potential therapeutic interventions. Further research into the differential regulation of HIF-1α in different cell types during ischemic stroke is crucial for understanding the disease mechanism and identifying novel treatment strategies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Medicinal
Jose M. Alonso, Alejandro Escobar-Peso, Alejandra Palomino-Antolin, Daniel Diez-Iriepa, Mourad Chioua, Emma Martinez-Alonso, Isabel Iriepa, Javier Egea, Alberto Alcazar, Jose Marco-Contelles
Summary: The article discusses the relationship between cerebrovascular diseases and dementia caused by Alzheimer's disease, highlighting the importance of developing new dual therapeutic agents. A new small quinolylnitrone, MC903, is proposed as a potential dual therapy for stroke and Alzheimer's disease.
Article
Food Science & Technology
Yujie Chen, Wuke Yuan, Qi Xu, Manju B. Reddy
Summary: Parkinson's disease (PD) and Alzheimer's disease (AD) are common neurodegenerative disorders with shared molecular mechanisms, and there is currently no effective treatment. However, research suggests that consuming phytochemicals may help delay the progression of these diseases.
JOURNAL OF FUNCTIONAL FOODS
(2023)
Article
Pharmacology & Pharmacy
Kemeng Zhao, Pengwei Wang, Xiaoguang Tang, Na Chang, Haonan Shi, Longfei Guo, Bingyi Wang, Pengfei Yang, Tiantian Zhu, Xinghua Zhao
Summary: Stroke is caused by ruptured or blocked cerebral blood vessels and subsequent disruption of brain blood circulation, resulting in rapid neurological deficits. The majority of stroke cases are ischemic strokes. Current treatments for ischemic stroke, such as t-PA thrombolytic therapy and surgical thrombectomy, can paradoxically lead to ischemia-reperfusion injury, exacerbating brain damage. Minocycline, a semi-synthetic tetracycline antibiotic, has demonstrated a wide range of neuroprotective effects independent of its antibacterial activity. In this article, we summarize the mechanisms underlying the protective effects of minocycline against cerebral ischemia-reperfusion injury, including modulation of oxidative stress, inflammatory response, excitotoxicity, programmed cell death, and blood-brain barrier injury. We also discuss the role of minocycline in alleviating stroke-related complications, providing a theoretical basis for its clinical application in cerebral ischemia-reperfusion injury.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Review
Cell Biology
Daryush Purrahman, Ali Shojaeian, Lukasz A. Poniatowski, Bartlomiej Piechowski-Jozwiak, Mohammad-Reza Mahmoudian-Sani
Summary: Stroke is a life-threatening condition and a major cause of disability. Cerebral ischemia triggers an inflammatory response involving various cytokines and inflammation-related agents. Progranulin (PGRN), a multifunctional protein, plays a critical role in physiological processes such as cell proliferation, inflammation, wound healing, and nervous system development. The mature form of PGRN has anti-inflammatory properties, while its derivative, granulin, induces pro-inflammatory cytokine expression. PGRN is significantly involved in brain tissue damage caused by conditions like cerebral ischemia, improving mood and cognitive disorders. It may also protect against nerve and spinal cord injuries by inhibiting neuroinflammatory response and apoptosis, as well as regulating microglia. PGRN acts as a neurotrophic factor in the central nervous system, promoting neurogenesis in the subventricular zone (SVZ) and improving long-term brain function after cerebral ischemia. The induction of PI3K/AKT and MAPK/ERK signaling pathways may contribute to PGRN-enhanced neurogenesis in the ischemic brain SVZ. Furthermore, PGRN can enhance the proliferation of neural stem/progenitor cells through the PI3K/AKT pathway. PGRN increases hippocampal neurogenesis, reducing anxiety and impaired spatial learning post-cerebral ischemia. PGRN alleviates cerebral ischemia/reperfusion injury by reducing endoplasmic reticulum stress and suppressing the NF-κB signaling pathway. Overall, PGRN is a potent neuroprotective agent that improves post-ischemia neuronal function by modulating inflammatory and anti-inflammatory cytokines.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Weilin Xu, Umut Ocak, Liansheng Gao, Sheng Tu, Cameron J. Lenahan, Jianmin Zhang, Anwen Shao
Summary: Autophagy is a fundamental process for clearing misfolded proteins and damaged organelles in cells, closely implicated in neurological diseases. Different types of selective autophagy are controlled by a group of important proteins, including PINK1, Parkin, and others, which are crucial for research on neurological diseases.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Matteo Haupt, Stefan T. Gerner, Mathias Baehr, Thorsten R. Doeppner
Summary: Ischemic stroke is a leading cause of death and disability globally, requiring urgent development of neuroprotective approaches due to limited treatment options. This study provides an overview of current research in neuroprotective stroke treatment, including traditional drugs targeting inflammation, cell death, and excitotoxicity, as well as stem-cell-based and extracellular vesicle-based methods. The review also discusses the potential of the microbiota-gut-brain axis as a target for future neuroprotective therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Carmen del Rio, Joan Montaner
Summary: Current therapies for stroke management are limited, as neuroprotective treatments have shown limited success due to the complex mechanisms of brain cell death in humans. However, various animal species demonstrate prolonged survival of neurons in hypoxic conditions, suggesting potential for new therapeutic approaches for stroke treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Agriculture, Multidisciplinary
Saurav Ghimire, Lalita Subedi, Namrata Acharya, Bhakta Prasad Gaire
Summary: Moringa oleifera, also known as a miracle tree or tree of life, has been used worldwide as a functional food and nutritional asset with various pharmacological activities, including neuroprotective effects against a range of diseases. Studies have isolated neuroprotective phytochemicals from M. oleifera, showing promising potential for neuroprotection.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Review
Neurosciences
Hao Tang, Jun Wen, Ting Qin, Yue Chen, Jiagui Huang, Qinghuan Yang, Peiran Jiang, Ling Wang, Yong Zhao, Qin Yang
Summary: Ischemic stroke is a leading cause of death and disability worldwide, but many patients are unable to receive current treatments due to limited treatment windows and complications. Sirt1 has emerged as a potential therapeutic target for ischemic stroke due to its neuroprotective properties. This review summarizes the evidence and mechanisms of Sirt1's role in providing neuroprotection against cerebral ischemic stroke. The review discusses Sirt1's protein structure, activation and inhibition, as well as its neuroprotective effects and specific mechanisms, such as inhibiting programmed cell death and promoting neurological repair.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Shu-na Wang, Zhi Wang, Xi-yuan Wang, Xiu-ping Zhang, Tian-ying Xu, Chao-yu Miao
Summary: This study establishes a humanized ischemic stroke model based on cerebral organoids (COs) and validates its sensitivity to ischemic injury and anti-stroke treatment.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Clinical Neurology
Shiyuan Fang, Xinzhi Hu, Tao Wang, Yutong Yang, Ran Xu, Xiao Zhang, Jichang Luo, Yan Ma, Aman B. Patel, Adam A. Dmytriw, Liqun Jiao
Summary: This study aimed to assess the potential causal association between Parkinson's disease (PD) and ischemic stroke (IS) using Mendelian randomization methods. The results showed that PD may be a potential cause of cardioembolic stroke and large artery stroke, but not small-vessel stroke.
TRANSLATIONAL STROKE RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Yue Liu, Liuding Wang, Guang Yang, Xiansu Chi, Xiao Liang, Yunling Zhang
Summary: Stroke is a leading cause of death and disability worldwide, with the majority of cases being ischemic stroke. The review highlights the role of sirtuins (SIRTs), a group of enzymes involved in various biological processes, in ischemic stroke. The review discusses the distribution, subcellular location, enzyme activity, and regulatory roles of SIRTs in ischemic stroke, as well as potential therapeutic methods based on SIRTs. The data collected in this study has potential implications for clinical and fundamental research on SIRTs and the development of effective therapeutic candidates for ischemic stroke treatment.
Article
Biochemistry & Molecular Biology
Yilong Zhao, Huajun Yang, Wei Shan, Anchen Guo, Qun Wang
Summary: Moderate ethanol preconditioning protects against ischemic brain injury by upregulating the expression of BKCa channels in rats.
NEUROCHEMICAL RESEARCH
(2022)
Review
Cell Biology
Sonia C. Correia, Paula I. Moreira
Summary: Oxygen sensing and homeostasis are crucial for brain integrity, especially in Alzheimer's disease where hypoxia and reduced cerebral blood flow exacerbate neurodegenerative events. Advanced neuroimaging tools have revealed the role of HIF signaling in the onset and progression of AD pathology, offering potential non-pharmacological and pharmacological strategies to target hypoxia and delay disease progression.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sonia C. Correia, Marco G. Alves, Pedro F. Oliveira, Gemma Casadesus, Joseph LaManna, George Perry, Paula I. Moreira
Summary: This study demonstrates that hypoxic preconditioning can prevent the sAD-like phenotype, partly by targeting mitochondria as a preventive strategy in the context of AD. Preconditioning with hypoxia enhances complex II-energized mitochondrial respiration in the hippocampus, improving mitochondrial function and mitochondrial DNA content. These findings provide a novel direction for hypoxic preconditioning as a preventive strategy for AD.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Biochemistry & Molecular Biology
Ana Catarina Pereira, Jessica De Pascale, Rosa Resende, Susana Cardoso, Isabel Ferreira, Bruno Miguel Neves, Mylene A. Carrascal, Monica Zuzarte, Nuno Madeira, Sofia Morais, Antonio Macedo, Analia do Carmo, Paula Moreira, Maria Teresa Cruz, Claudia F. Pereira
Summary: This study aimed to investigate the role of ER-mitochondria communication in ER stress-induced NLRP3 inflammasome activation. The results showed that ER stress can activate NLRP3 inflammasome by a Ca2+-dependent and ROS-independent mechanism, which is associated with upregulation of MAMs-resident chaperones, increased ER-mitochondria contacts, and mitochondrial depolarization and impaired dynamics. Moreover, enhanced ER stress-induced NLRP3 inflammasome activation is associated with immune system abnormalities in various diseases.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Antonia Diniz, Marco G. Alves, Emanuel Candeias, Ana I. Duarte, Paula I. Moreira, Branca M. Silva, Pedro F. Oliveira, Luis Rato
Summary: Type 2 diabetes disrupts the SIRT1/PGC-1 alpha/SIRT3 pathway in the epididymis, leading to compromised mitochondrial function and decreased antioxidant defenses. This results in increased oxidative damage and impaired male reproductive function in diabetic men.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Hugo Ferreira, Pedro Serranho, Pedro Guimaraes, Rita Trindade, Joao Martins, Paula Moreira, Antonio Francisco Ambrosio, Miguel Castelo-Branco, Rui Bernardes
Summary: The early diagnosis of neurodegenerative disorders, especially Alzheimer's disease, remains a challenge. This study trained a convolution neural network using a mouse model to diagnose AD through fundus images with promising accuracy.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Cristina Carvalho, Sonia C. Correia, Raquel Seica, Paula Moreira
Summary: This study aimed to evaluate the role of WWOX activation in high glucose-induced neuronal damage and death. The results showed that WWOX activation is associated with mitochondrial dysfunction, cell damage, and death under high glucose conditions, suggesting that WWOX could be a potential therapeutic target for early interventions.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Neurosciences
Cristina Carvalho, Paula I. Moreira
Summary: Type 2 diabetes (T2D) and Alzheimer's disease (AD) are both global epidemics with shared metabolic defects and increased risk of cognitive decline and dementia. This article provides an overview of the metabolic defects that characterize and link both diseases, with a focus on mitochondria. The potential biomarkers and therapeutic drugs targeting mitochondria are also briefly discussed.
CURRENT OPINION IN NEUROBIOLOGY
(2023)
Review
Pharmacology & Pharmacy
Judite R. M. Coimbra, Paula I. Moreira, Armanda E. Santos, Jorge A. R. Salvador
Summary: This review explores the biological functions and structures of QPCT/L enzymes, highlights their therapeutic relevance, and summarizes recent developments in the discovery of small-molecule inhibitors targeting these enzymes.
DRUG DISCOVERY TODAY
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Brigida R. Pinho, Ana I. Duarte, Paula M. Canas, Paula I. Moreira, Michael P. Murphy, Jorge M. A. Oliveira
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Geriatrics & Gerontology
Ana Batista, Pedro Guimaraes, Joao Martins, Paula I. Moreira, Antonio Francisco Ambrosio, Miguel Castelo-Branco, Pedro Serranho, Rui Bernardes
Summary: Animal models are crucial for understanding retinal development, eye diseases, and neurodegeneration. In this study, a comprehensive normative database of retinal thickness in mice was created using OCT data. The findings revealed changes in retinal thickness over time, with different patterns among individual retinal layers. Additionally, a comparison between wild-type and Alzheimer's disease model mice showed significant differences in retinal thickness. This database will be an important reference for future studies on retinal changes and the pathophysiology of neurodegenerative and eye diseases.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Review
Biology
Tania Fernandes, M. Rosario Domingues, Paula I. Moreira, Claudia F. Pereira
Summary: Neurodegenerative diseases affect millions of people worldwide, but currently there is no cure for these disorders. Research on the endoplasmic reticulum-mitochondria interaction, called mitochondria-associated membranes (MAMs), is gaining attention in understanding the role of lipid metabolism in neurodegeneration. MAMs are involved in lipid synthesis, transport, and degradation, and changes in lipid metabolism can contribute to the development of neurodegenerative diseases. This review highlights the importance of lipid metabolism and MAMs in neurodegenerative disorders.
Review
Biochemistry & Molecular Biology
Tiago Sousa, Paula I. Moreira, Susana Cardoso
Summary: Alzheimer's disease is a prevalent neurodegenerative disorder without an effective treatment. Dysfunction of mitochondria has been found in AD, and restoring their function may be a crucial strategy for tackling the disease.
Meeting Abstract
Medicine, General & Internal
C. Carvalho, S. C. Correia, S. Cardoso, P. I. Moreira
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biochemistry & Molecular Biology
Pei-Yang Gao, Ya-Nan Ou, Yi-Ming Huang, Zhi-Bo Wang, Yan Fu, Ya-Hui Ma, Qiong-Yao Li, Li-Yun Ma, Rui-Ping Cui, Yin-Chu Mi, Lan Tan, Jin-Tai Yu
Summary: Liver function may play a role in the progression of Alzheimer's disease. The study found that as AD progressed, certain liver function markers increased while others decreased. The relationship between liver function and CSF AD biomarkers indicates a potential mediation effect on cognition.
JOURNAL OF NEUROCHEMISTRY
(2024)
