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
Anton N. Shuvaev, Olga S. Belozor, Oleg Mozhei, Elena D. Khilazheva, Andrey N. Shuvaev, Yana Fritsler, S. Kasparov
Summary: Spinocerebellar ataxias are fatal inherited diseases affecting the brain, with potential treatment using memantine. Research showed memantine can prevent cerebellar glial cell pathology and protect neurons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Shilpa Kumari, Rahul Deshmukh
Summary: Alzheimer's disease is a multifactorial disorder with accumulation of A beta and neurofibrillary tangles. Although new drug targets are being explored, the lengthy and expensive drug development process hinders fast translation of therapeutic outcomes. Repurposing existing drugs is considered a better approach for faster therapeutic information translation.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Wei Yuan, Liaoxun Lu, Muding Rao, Yang Huang, Chun-E Liu, Shuang Liu, Yue Zhao, Huicong Liu, Jiangli Zhu, Tianzhu Chao, Can Wu, Junyan Ren, Luxian Lv, Wenqiang Li, Shiqian Qi, Yinming Liang, Shijing Yue, Jian Gao, Zhongjian Zhang, Eryan Kong
Summary: Palmitoylation and depalmitoylation homeostasis is crucial for proper physiological functions, particularly in the central nervous system (CNS). GFAP is readily palmitoylated in vitro and in vivo, with palmitoylated GFAP promoting astrocyte proliferation. PPT1 depalmitoylates GFAP, and elevated levels of palmitoylated GFAP in PPT1-knockin mice may accelerate astrocyte proliferation and contribute to astrogliosis in INCL.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Brian M. Polster, Karla A. Mark, Rafael Arze, Derek Hudson
Summary: Glutamate excitotoxicity contributes to neurodegenerative diseases by causing calcium deregulation and mitochondrial depolarization. The experiment shows that glutamate increases protease activity in neurons before calcium deregulation, and this increase can be suppressed by glutamate receptor antagonists but not by calpain.
Article
Neurosciences
Theresa S. Rimmele, Shaomin Li, Jens Velde Andersen, Emil W. Westi, Alexander Rotenberg, Jianlin Wang, Blanca Irene Aldana, Dennis J. Selkoe, Chiye J. Aoki, Chris G. Dulla, Paul Allen Rosenberg
Summary: The major glutamate transporter GLT-1 is expressed in both presynaptic terminals and astrocytes in the mammalian central nervous system. While astrocytic GLT-1 is believed to primarily regulate glutamate homeostasis, the function of neuronal GLT-1 has remained relatively unexplored. Conditional knockout of GLT-1 in neurons resulted in impaired stimulus-evoked field extracellular postsynaptic potentials (fEPSPs), suggesting a crucial role for neuronal GLT-1 in excitatory synaptic transmission. Excitotoxicity may underlie the transmission failure observed in neuronal GLT-1 knockout mice, with potential metabolic perturbations contributing to vulnerability to NMDA receptor activation.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Environmental Sciences
Cheng Zhang, Yanyao Li, Haibo Yu, Limin Ye, Tian Li, Xiaotian Zhang, Chi Wang, Pengju Li, Hong Ji, Qinfeng Gao, Shuanglin Dong
Summary: This study found that nanoplastics promote the accumulation of arsenic in zebrafish brains, leading to severe oxidative stress and mitochondrial damage, ultimately affecting neurological function and causing cell apoptosis. This study provides a risk assessment for evaluating the biotoxicity of nanoplastics and arsenic to fish and other animals.
SCIENCE OF THE TOTAL ENVIRONMENT
(2023)
Review
Biochemistry & Molecular Biology
Jens V. Andersen, Arne Schousboe
Summary: Since the recognition of glutamate and GABA as principal neurotransmitters, significant discoveries have been made about their synaptic homeostasis. The glutamate/GABA-glutamine cycle, involving the recycling between neurons and astrocytes, plays a crucial role in maintaining synaptic transmission. The metabolic function of neurons and astrocytes is closely related to the glutamate/GABA-glutamine cycle, with astrocytes providing metabolic support for neurons. The review focuses on cellular uptake, metabolism, and recycling of glutamate and GABA, as well as their role in brain pathology and the potential of targeting astrocyte metabolism for intervention.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Neurosciences
Jessica Proulx, Satomi Stacy, In-Woo Park, Kathleen Borgmann
Summary: Astrocytes are essential for maintaining the health and function of the central nervous system, but their functions can become dysregulated during HIV-1 infection and chronic METH exposure. This study identified IRE1α as a key regulator of astrocyte mitochondrial dysfunction and suggests it as a potential target for regulating astrocyte dysfunction.
FRONTIERS IN NEUROSCIENCE
(2022)
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)
Article
Neurosciences
Emil W. Westi, Emil Jakobsen, Caroline M. Voss, Lasse K. Bak, Lars H. Pinborg, Blanca Aldana, Jens Andersen
Summary: Differences in cellular composition and structure may influence the metabolism of rodent and human brain. Human cerebral slices have lower metabolic rates but higher coupled respiration and more efficient mitochondrial coupling compared to mouse slices.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Adelheid Weidinger, Nadja Milivojev, Arthur Hosmann, J. Catharina Duvigneau, Csaba Szabo, Gabor Toro, Laurin Rauter, Annette Vaglio-Garro, V. Garik Mkrtchyan, Lidia Trofimova, Rinat R. Sharipov, Alexander M. Surin, Irina A. Krasilnikova, Vsevolod G. Pinelis, Laszlo Tretter, Rudolf Moldzio, Hulya Bayir, Valerian E. Kagan, Victoria I. Bunikg, Andrey V. Kozlov
Summary: Brain injury leads to neuroinflammation, extracellular glutamate accumulation, and mitochondrial dysfunction, causing neuronal death. This study aimed to investigate the effects of these mechanisms on neuronal death. Patients with aneurysmal subarachnoid hemorrhage (SAH) were recruited from a neurosurgical intensive care unit, and in vitro experiments were performed using rat cortex homogenate, neuronal cultures, and cell lines. The results showed that elevated levels of extracellular glutamate and nitric oxide (NO) metabolites were associated with poor clinical outcome in SAH patients. Inhibition of the key enzyme OGDHC from the glutamate-dependent segment of the tricarboxylic acid cycle by NO led to extracellular glutamate accumulation and neuronal death. However, reactivation of OGDHC by its cofactor thiamine reduced extracellular glutamate levels and protected against glutamate toxicity.
Article
Immunology
Elizabeth E. Evans, Vikas Mishra, Crystal Mallow, Elaine M. Gersz, Leslie Balch, Alan Howell, Christine Reilly, Ernest S. Smith, Terrence L. Fisher, Maurice Zauderer
Summary: SEMA4D is upregulated in neurons during neurodegenerative diseases and triggers reactive astrocytes. Blocking SEMA4D preserves normal astrocyte function and reduces the negative consequences of reactive astrogliosis.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Multidisciplinary Sciences
Bryan A. Killinger, Lee L. Marshall, Diptaman Chatterjee, Yaping Chu, Jose Bras, Rita Guerreiro, Jeffrey H. Kordower
Summary: This study used biotinylation by antibody recognition (BAR) to label pathological alpha-synuclein and performed mass spectrometry analysis on Lewy pathology (LP). It identified 261 enriched proteins in synucleinopathy brains and revealed PD as the most significant pathway. BAR has the potential to help understand LP in primary human tissue and animal models.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Pharmacology & Pharmacy
Wolfgang Loescher, Pavel Klein
Summary: The prevailing standard in drug discovery has shifted from designing highly selective compounds to multi-target and combinatorial drug therapies. Although drug combination therapy is effective for symptomatic treatment, identifying clinically effective disease-modifying treatments for complex brain diseases remains challenging.
PHARMACOLOGY & THERAPEUTICS
(2022)