Article
Biochemistry & Molecular Biology
Ashwini Sri Hari, Rajeswari Banerji, Li -Ping Liang, Ruth E. Fulton, Christopher Quoc Huynh, Timothy Fabisiak, Pallavi Bhuyan Mcelroy, James R. Roede, Manisha Patel
Summary: Elevation of glutathione (GSH) levels has been shown to decrease oxidative stress and seizure frequency, as well as rescue cognitive deficits in epilepsy. Treatment with dimercaprol (DMP), which increases cellular GSH, inhibits neuronal hyperexcitability and reduces seizures in vitro and in vivo. The redox-sensitive mTORC1 pathway may be a plausible link between GSH elevation and inhibition of neuronal hyperexcitability.
Article
Chemistry, Multidisciplinary
Ashim Paul, Sourav Kumar, Sujan Kalita, Sourav Kalita, Dibakar Sarkar, Anirban Bhunia, Anupam Bandyopadhyay, Amal Chandra Mondal, Bhubaneswar Mandal
Summary: Synthetic antibodies show great promise in combating diseases and biomedical applications, but designing a therapeutic synthetic antibody to prevent amyloid-beta aggregation remains challenging. A novel synthetic paratope, SP1, has been reported to prevent A beta aggregation, reverse amyloid fibrils, and reduce neurotoxicity in human cells. This new paratope engineering module may lead to cost-effective molecular probes for combating protein misfolding-related diseases.
Article
Neurosciences
Yao Cheng, Yujie Zhai, Yi Yuan, Hao Li, Wenke Zhao, Zhenhai Fan, Ling Zhou, Xue Gao, Yan Zhan, Hongliu Sun
Summary: This study evaluates the effectiveness of xenon in treating prolonged febrile seizures and preventing epilepsy. The results suggest that xenon treatment can alleviate the damage caused by prolonged febrile seizures and reduce the risk of developing epilepsy.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Genetics & Heredity
Jyotsna Kumar, Michael Reidy, Daniel C. Masison
Summary: The study reveals that when Sis1JGF replaces Sis1, Sup35 is less soluble and forms visibly larger prion aggregates in [PSI+] cells. Additionally, exogenous expression of a truncated form of Sup35 that cannot incorporate into prions alleviates the toxicity of [PSI+].
Article
Microbiology
Patricia Aguilar-Calvo, Adela Malik, Daniel R. Sandoval, Christopher Barback, Christina D. Orru, Heidi G. Standke, Olivia R. Thomas, Chrissa A. Dwyer, Donald P. Pizzo, Jaidev Bapat, Katrin Soldau, Ryotaro Ogawa, Mckenzie B. Riley, K. Peter R. Nilsson, Allison Kraus, Byron Caughey, Jeffrey J. Iliff, David R. Vera, Jeffrey D. Esko, Christina J. Sigurdson
Summary: In this study, the effect of HS sulfation on the growth of prion fibrillar plaques in the brain was investigated. The results showed that reducing HS sulfation prolonged survival and reduced the size and number of plaques in mice infected with plaque-forming prions. Live imaging also revealed that unsulfated HS facilitated the clearance of prion protein monomers from the brain.
Article
Neurosciences
Ali A. Alshamrani, James L. Franklin
Summary: This study investigated the protective effect of elevated extracellular potassium ([K+](E)) on NGF-deprived sympathetic neurons, showing that [K+](E) primarily prevents apoptosis through an antioxidant mechanism and partially through the inhibition of upregulation of BIMEL. Additionally, it was found that [K+](E) increased cellular antioxidant glutathione levels, leading to the prevention of cytochrome c release and cell death.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Teruhiko Matsubara, Mako Nakai, Masaya Nishihara, Erika Miyamoto, Toshinori Sato
Summary: The ganglioside cluster-binding peptide inhibits the formation of amyloid fi protein (Afi) assemblies and removes Afi fibrils deposited on the lipid membrane, showing potential as a novel Afi-targeting drug to ameliorate Alzheimer's disease (AD).
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Anna Chang, Yi Chang, Su-Jane Wang
Summary: This study investigated the potential antiseizure mechanisms of rutin in rats using the kainic acid (KA) seizure model. The results indicate that rutin attenuated seizure severity and neuronal loss by decreasing glutamatergic hyperactivity and suppressing the neuroinflammatory cascade.
Article
Chemistry, Multidisciplinary
Hye Joung Choi, Tong-xiang Chen, Ming-Jie Hou, Ji Hoon Song, Peng Li, Chun-feng Liu, Pan Wang, Bao Ting Zhu
Summary: This study found that norepinephrine and dopamine can slow the progression of oxidative neurodegeneration by inhibiting protein disulfide isomerase. These neurotransmitters can protect neuronal cells from oxidative damage by suppressing mitochondrial dysfunction and related signaling pathways.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Biotechnology & Applied Microbiology
Yunxiao Dou, Junchao Xie, Yan Tan, Min Zhang, Yanxin Zhao, Xueyuan Liu
Summary: The balance of excitatory and inhibitory neurotransmitters can affect the impact of neuron-released extracellular vesicles on amyloid beta toxicity in Alzheimer's disease.
JOURNAL OF NANOBIOTECHNOLOGY
(2021)
Article
Geriatrics & Gerontology
Firat Kara, James M. Joers, Dinesh K. Deelchand, Young Woo Park, Scott A. Przybelski, Timothy G. Lesnick, Matthew L. Senjem, Burcu Zeydan, David S. Knopman, Val J. Lowe, Prashanthi Vemuri, Michelle M. Mielke, Mary M. Machulda, Clifford R. Jack, Ronald C. Petersen, Gulin Oz, Kejal Kantarci
Summary: Proton magnetic resonance spectroscopy (H-1 MRS) provides information on pathophysiological changes in Alzheimer's disease. This study found that increased posterior cingulate gyrus tau deposition in cognitively unimpaired older adults is associated with biomarkers of neural and synaptic injury, which appears to be stronger in women.
NEUROBIOLOGY OF AGING
(2022)
Article
Biology
Chatrawee Duangjan, Panthakarn Rangsinth, Shaoxiong Zhang, Xiaojie Gu, Michael Wink, Tewin Tencomnao
Summary: The GZM extract demonstrated neuroprotective effects by suppressing ROS generation and enhancing antioxidant enzyme expression in cultured neuronal cells. It also triggered the expression of SIRT1/Nrf2 proteins and antioxidant genes, showing promising potential for treating oxidative stress-induced neurodegenerative diseases like Alzheimer's.
Article
Biotechnology & Applied Microbiology
Yan-Zhong Wu, Chun-Lin Lee
Summary: The study demonstrated that deep ocean water-cultured Cordyceps cicadae had a significant effect on improving memory deficit in Alzheimer's disease rats by suppressing risk factors expressions induced by Aβ40 and streptozotocin.
FERMENTATION-BASEL
(2021)
Article
Neurosciences
Chao Tai, Che-Wei Chang, Gui-Qiu Yu, Isabel Lopez, Xinxing Yu, Xin Wang, Weikun Guo, Lennart Mucke
Article
Biology
Javier Diaz-Alonso, Wade Morishita, Salvatore Incontro, Jeffrey Simms, Julia Holtzman, Michael Gill, Lennart Mucke, Robert C. Malenka, Roger A. Nicoll
Review
Multidisciplinary Sciences
Che-Wei Chang, Eric Shao, Lennart Mucke
Summary: Evidence suggests that the protein tau plays a role in the pathogenesis of various brain disorders, but the specific functions and contributions of abnormal tau species in different disease models pose challenges to developing effective therapeutic strategies.
Article
Neurosciences
Daniel R. Gulbranson, Kaitlyn Ho, Gui-Qiu Yu, Xinxing Yu, Melanie Das, Eric Shao, Daniel Kim, Weiping J. Zhang, Krishna Choudhary, Reuben Thomas, Lennart Mucke
Summary: This study demonstrates that the insertional mutation in hAPP-J20 mice does not account for the Alzheimer's disease (AD)-like phenotype of this model. Furthermore, neural development and brain functions are well preserved in Zbtb20(+/-) mice when Zbtb20 levels are reduced by half.
Article
Neurosciences
Erik C. B. Johnson, E. Kathleen Carter, Eric B. Dammer, Duc M. Duong, Ekaterina S. Gerasimov, Yue Liu, Jiaqi Liu, Ranjita Betarbet, Lingyan Ping, Luming Yin, Geidy E. Serrano, Thomas G. Beach, Junmin Peng, Philip L. De Jager, Vahram Haroutunian, Bin Zhang, Chris Gaiteri, David A. Bennett, Marla Gearing, Thomas S. Wingo, Aliza P. Wingo, James J. Lah, Allan I. Levey, Nicholas T. Seyfried
Summary: This study analyzed the proteomes of over 1,000 brain tissues and identified new protein co-expression modules associated with Alzheimer's disease. These modules were highly conserved across cohorts and brain regions and revealed a proteopathic nature of the disease. The study also found disease-associated modules unique to the proteome, which could serve as potential therapeutic targets and biomarkers for Alzheimer's disease.
NATURE NEUROSCIENCE
(2022)
Article
Cell Biology
Che-Wei Chang, Mark D. Evans, Xinxing Yu, Gui-Qiu Yu, Lennart Mucke
Summary: The protein tau plays a crucial role in brain disorders, and reducing its levels can prevent network hypersynchrony and counteract brain disorders with abnormally increased excitation-inhibition ratios.
Article
Clinical Neurology
Keith Vossel, Kamalini G. Ranasinghe, Alexander J. Beagle, Alice La, Kasey Ah Pook, Madelyn Castro, Danielle Mizuiri, Susanne M. Honma, Nisha Venkateswaran, Mary Koestler, Wenbo Zhang, Lennart Mucke, Michael J. Howell, Katherine L. Possin, Joel H. Kramer, Adam L. Boxer, Bruce L. Miller, Srikantan S. Nagarajan, Heidi E. Kirsch
Summary: The study demonstrated that treatment with levetiracetam improved spatial memory and executive function tasks in patients with Alzheimer's disease and epileptiform activity, suggesting the need for further assessment of antiseizure approaches in AD.
Article
Multidisciplinary Sciences
Hazal Haytural, Rui Benfeitas, Sophia Schedin-Weiss, Erika Bereczki, Melinda Rezeli, Richard D. Unwin, Xusheng Wang, Eric B. Dammer, Erik C. B. Johnson, Nicholas T. Seyfried, Bengt Winblad, Betty M. Tijms, Pieter Jelle Visser, Susanne Frykman, Lars O. Tjernberg
Summary: Through meta-analysis of high-quality proteomic studies, consistent pathological changes in Alzheimer's disease were revealed, particularly involving dysregulation of pathways related to synaptic signaling, oxidative phosphorylation, immune response, and extracellular matrix.
Article
Multidisciplinary Sciences
Melanie Das, Wenjie Mao, Eric Shao, Soniya Tamhankar, Gui-Qiu Yu, Xinxing Yu, Kaitlyn Ho, Xin Wang, Jiaming Wang, Lennart Mucke
Summary: Nonconvulsive epileptiform activity and microglial alterations have been detected in individuals with Alzheimer's disease (AD) and related mouse models. Suppressing epileptiform activity reversed or prevented aberrant microglial gene expression, including modulation of key factors like TREM2, which seems to support microglial activities counteracting network dysfunction.
Article
Cell Biology
Eric Shao, Che-Wei Chang, Zhiyong Li, Xinxing Yu, Kaitlyn Ho, Michelle Zhang, Xin Wang, Jeffrey Simms, Iris Lo, Jessica Speckart, Julia Holtzman, Gui-Qiu Yu, Erik D. Roberson, Lennart Mucke
Summary: This study found that reducing TAU in excitatory neurons can alleviate various brain dysfunctions, including epilepsy and overactivation of the phosphoinositide 3-kinase-AKT-mammalian target of rapamycin pathway, in a mouse model of Dravet syndrome. Additionally, treatment with a TAU-lowering antisense oligonucleotide had similar therapeutic effects.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Chemistry, Medicinal
Robert A. Craig II, Brian M. Fox, Cheng Hu, Katrina W. Lexa, Maksim Osipov, Arun P. Thottumkara, Martin Larhammar, Takashi Miyamoto, Anil Rana, Lesley A. Kane, Ernie Yulyaningsih, Hilda Solanoy, Hoang Nguyen, Roni Chau, Timothy Earr, Yuji Kajiwara, Daniel Fleck, Anthony Lucas, Patrick C. G. Haddick, Ryan H. Takahashi, Vincent Tong, Jing Wang, Mark J. Canet, Suresh B. Poda, Kimberly Scearce-Levie, Ankita Srivastava, Zachary K. Sweeney, Musheng Xu, Rui Zhang, Jianrong He, Yanan Lei, Zheng Zhuo, Javier de Vicente
Summary: This study identified novel inhibitors of dual leucine zipper kinase/leucine zipper-bearing kinase through drug design approaches. The identified inhibitor demonstrated excellent pharmacokinetic properties and therapeutic potential in in vivo and in vitro studies.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Clinical Neurology
Eric B. Dammer, Lingyan Ping, Duc M. Duong, Erica S. Modeste, Nicholas T. Seyfried, James J. Lah, Allan Levey, Erik C. B. Johnson
Summary: Robust and accessible biomarkers are urgently needed for the study of Alzheimer's disease. The study found correlations between protein markers in CSF and plasma, with greater variability in plasma. Proteomic analysis revealed changes in protein co-expression modules related to autophagy, ubiquitination, sugar metabolism, and other processes.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Article
Multidisciplinary Sciences
Caroline M. Watson, Eric B. Dammer, Lingyan Ping, Duc M. Duong, Erica Modeste, E. Kathleen Carter, Erik C. B. Johnson, Allan I. Levey, James J. Lah, Blaine R. Roberts, Nicholas T. Seyfried
Summary: Alzheimer's disease (AD) is the most common form of dementia, and CSF beta-amyloid, total Tau, and phosphorylated Tau (pTau) are sensitive and specific biomarkers for diagnosis. However, these biomarkers do not capture the complex changes in AD brain beyond amyloid and Tau pathologies. This study used SRM-MS with isotopically labeled standards to quantify CSF protein biomarkers, identifying proteins that could distinguish AD stages and cognitive impairment.
Article
Cell Biology
Rafi Haque, Caroline M. Watson, Jiaqi Liu, E. Kathleen Carter, Duc M. Duong, James J. Lah, Aliza P. Wingo, Blaine R. Roberts, Erik C. B. Johnson, Andrew J. Saykin, Leslie M. Shaw, Nicholas T. Seyfried, Thomas S. Wingo, Allan I. Levey
Summary: This study developed a reliable and high-throughput mass spectrometry assay to detect 48 key proteins in cerebrospinal fluid (CSF), and found that this panel of proteins performed at least as well as existing biomarkers in predicting clinical diagnosis, brain imaging results, cognitive decline, and dementia severity in Alzheimer's disease. Combining this panel with existing biomarkers significantly improved diagnostic accuracy and prediction of disease progression.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Marta del Campo, Carel F. W. Peeters, Erik C. B. Johnson, Lisa Vermunt, Yanaika S. Hok-A-Hin, Mirrelijn van Nee, Alice Chen-Plotkin, David J. Irwin, William T. Hu, James J. Lah, Nicholas T. Seyfried, Eric B. Dammer, Gonzalo Herradon, Lieke H. Meeter, John van Swieten, Daniel Alcolea, Alberto Lleo, Allan I. Levey, Afina W. Lemstra, Yolande A. L. Pijnenburg, Pieter J. Visser, Betty M. Tijms, Wiesje M. van der Flier, Charlotte E. Teunissen
Summary: This study identifies specific dysregulated CSF proteins along the AD continuum, reflecting the multifactorial nature of disease progression. Some of these dysregulated proteins can be used as biomarkers for the diagnosis and clinical trials of AD.