Results 41 to 50 of about 19,301 (220)

Lilrb4a Suppression Reprograms Microglia to Mitigate APOE4‐Associated Amyloid Plaques and Cerebral Amyloid Angiopathy in Association With a PPAR‐Linked Pro‐Clearance State

Advanced Science, EarlyView.
Targeting Lilrb4a in Apolipoprotein E4 (APOE4)‐associated Alzheimer's disease (AD) reprograms microglia toward a beneficial, phagocytic state. Genetic deletion or antisense inhibition of Lilrb4a suppresses p‐SHP2/NF‐κB/STAT1 signaling, restores PPAR‐linked lipid and energy metabolism, and reduces amyloid plaque burden and cerebral amyloid angiopathy ...
Changxu Nie, Ruixi Yang, Xiaotong Wang, Ping Jia, Xueqi Zhang, Yaqi Dai, Xue Bai, Sijia Duan, Yufeng Li, Peng Zheng, Xin Tian, Li Jiang, Chao Wang   +12 more
wiley   +1 more source

Comparison of Common and Disease-Specific Post-translational Modifications of Pathological Tau Associated With a Wide Range of Tauopathies

Frontiers in Neuroscience, 2020
Tauopathies are the most common type of neurodegenerative proteinopathy, being characterized by cytoplasmic aggregates of hyperphosphorylated tau protein. The formation and morphologies of these tau inclusions, the distribution of the lesions and related
Fuyuki Kametani, Mari Yoshida, Tomoyasu Matsubara, Shigeo Murayama, Yuko Saito, Ito Kawakami, Mitsumoto Onaya, Hidetomo Tanaka, Akiyoshi Kakita, Andrew C. Robinson, David M. A. Mann, Masato Hasegawa   +11 more
doaj   +1 more source

A Phase‐Resolved Geometric Deep Learning Framework Maps Structural Determinants of Disease‐Associated Protein Aggregation and Guides Suppressor Design

Advanced Science, EarlyView.
SKALE 2.0 maps disease‐associated protein aggregation as a phase‐resolved structural process, linking mutation‐induced geometric perturbations to nucleation, elongation, and suppressor design. Across neurodegenerative proteins, the framework reveals cryptic aggregation vulnerabilities, separates phase‐concordant and phase‐switching mutations, and ...
Jia Shen Sio, Wei Xuan Wilson Loo, Yan Shan Loo, Wen Xin Tan, Hui Xuan Lim, Huitao Liu, Chen Seng Ng   +6 more
wiley   +1 more source

CHCHD10 Mitigates Alzheimer's Disease‐Related Phenotypes in Association With Epigenetic Remodeling in Directly Reprogrammed Neurons

Advanced Science, EarlyView.
CHCHD10 loss in Alzheimer's disease is associated with mitochondrial dysfunction, epigenomic disruption, and tau pathology. Restoration of CHCHD10 shifts DNA methylation toward a non‐disease state and reduces tau and amyloid pathology, with KATNAL2 acting as a downstream effector.
Teresa M. Thomas, Ching‐Yao Yang, Kexin Zhang, Liam Wetzel, Dina Bugybayeva, Julia Ferguson, Md Mahmudul Hasan, William Samsa, Nandita Patil, Anshul Dash, Tarini Gowda, Xiongwei Zhu, Feixiong Cheng, Tian Liu   +13 more
wiley   +1 more source

Neuron‐Targeted Exosomal Delivery of siRNA Against RIPK3 Slows Neurodegenerative Progression in Alzheimer's Disease

Advanced Science, EarlyView.
Engineered exosomal siRNA delivery platform enables systemic, neuron‐targeted RNA transport across the blood–brain barrier. Surface functionalization with rabies virus glycoprotein‐derived peptide facilitates receptor‐mediated transcytosis, achieving efficient cytosolic delivery and robust gene silencing. Targeting RIPK3 suppresses necroptosis, reduces
Chi Zhang, Jiaqi Zhang, Yuzhi Wang, Yaodong Wang, Peng Lin, Yanling Wang, Zixuan Tang, Jintai Yu, Qin Zhou, Feiyun Cui   +9 more
wiley   +1 more source

Novel aspects of the phosphorylation and structure of pathological tau: implications for tauopathy biomarkers

FEBS Open Bio
The deposition of highly phosphorylated and aggregated tau is a characteristic of tauopathies, including Alzheimer's disease. It has long been known that different isoforms of tau are aggregated in different cell types and brain regions in each tauopathy.
Taeko Kimura, Haruaki Sato, Maria Kano, Lisa Tatsumi, Taisuke Tomita   +4 more
doaj   +1 more source

Therapeutic Gene Editing of APOE4 in Sporadic Alzheimer's Disease via Prime Editor 7

Advanced Science, EarlyView.
Prime Editor 7‐mediated conversion of APOE4 to APOE3 alleviates Alzheimer's disease‐associated pathology in AD mouse models and patient‐derived neurons and improves cognitive performance in vivo, supporting therapeutic genome editing as a promising strategy for APOE4‐associated neurodegeneration.
Yunkyung Kim, Gaeun Lee, Saemin An, Hanseul Park, Hongwon Kim, Jisung Kim, Soi Kang, Sumin Kim, Daeyeol Kwon, Jeonghyun Park, Yerim Hwang, Seonghun Kim, Xiuwen Yuan, Jaehoon Jeong, Hamin Lee, Hui Kwon Kim, Jongpil Kim   +16 more
wiley   +1 more source

Endoplasmic reticulum unfolded protein response transcriptional targets of XBP-1s mediate rescue from tauopathy

Communications Biology
Pathological tau disrupts protein homeostasis (proteostasis) within neurons in Alzheimer’s disease (AD) and related disorders. We previously showed constitutive activation of the endoplasmic reticulum unfolded protein response (UPRER) transcription ...
Sarah M. Waldherr, Marina Han, Aleen D. Saxton, Taylor A. Vadset, Pamela J. McMillan, Jeanna M. Wheeler, Nicole F. Liachko, Brian C. Kraemer   +7 more
doaj   +1 more source

PD-1/PD-L1 checkpoint blockade harnesses monocyte-derived macrophages to combat cognitive impairment in a tauopathy mouse model

Nature Communications, 2019
Blocking the PD-1 pathway was shown to be effective in amyloid beta mouse models, yet little is known about its therapeutic potential in models of tauopathy.
Neta Rosenzweig, Raz Dvir-Szternfeld, Afroditi Tsitsou-Kampeli, Hadas Keren-Shaul, Hila Ben-Yehuda, Pierre Weill-Raynal, Liora Cahalon, Alex Kertser, Kuti Baruch, Ido Amit, Assaf Weiner, Michal Schwartz   +11 more
doaj   +1 more source

Possible Mechanisms of Tau Spread and Toxicity in Alzheimer’s Disease

Frontiers in Cell and Developmental Biology, 2021
Tau is a protein that associates with microtubules (MTs) and promotes their assembly and stability. The protein loses its ability to bind MTs in tauopathies, and detached tau can misfold and induce the pathological changes that characterize Alzheimer’s ...
Huiqin Zhang, Yu Cao, Lina Ma, Yun Wei, Hao Li   +4 more
doaj   +1 more source