Review
Geriatrics & Gerontology
Jiang Chen, Jun-Sheng Chen, Song Li, Fengning Zhang, Jie Deng, Ling-Hui Zeng, Jun Tan
Summary: Decades of research have shown that amyloid-beta (Aβ) plays an undeniable role in the development of Alzheimer's disease (AD). However, the focus on the pathological effects of Aβ may overshadow the significance of its metabolic precursor, amyloid precursor protein (APP), in the occurrence and progression of AD. This review explores the various roles of APP in AD, including its structure, functions, enzymatic processing, and potential therapeutic approaches to targeting APP to ameliorate AD pathologies and halt disease progression.
Article
Neurosciences
Sandra Schilling, Ajay Pradhan, Amelie Heesch, Andrea Helbig, Kaj Blennow, Christian Koch, Lea Bertgen, Edward H. Koo, Gunnar Brinkmalm, Henrik Zetterberg, Stefan Kins, Simone Eggert
Summary: This study compares the effects of different APP genetic mutations on their processing and pathogenic mechanisms in Alzheimer's disease. The results show significant differences in the underlying mechanisms for familial AD mutations located at the alpha-, beta-, and gamma-secretase cleavage sites. Different mutations have different effects on APP processing and the generation of A β peptides.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Zdenek Fisar
Summary: Damage or loss of brain cells and impaired neurochemistry, neurogenesis, and synaptic and nonsynaptic plasticity of the brain lead to dementia in neurodegenerative diseases, such as Alzheimer's disease (AD). Injury to synapses and neurons and accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles are considered the main morphological and neuropathological features of AD. Age, genetic and epigenetic factors, environmental stressors, and lifestyle contribute to the risk of AD onset and progression. These risk factors are associated with structural and functional changes in the brain, leading to cognitive decline. Biomarkers of AD reflect or cause specific changes in brain function, especially changes in pathways associated with neurotransmission, neuroinflammation, bioenergetics, apoptosis, and oxidative and nitrosative stress. Even in the initial stages, AD is associated with A beta neurotoxicity, mitochondrial dysfunction, and tau neurotoxicity. The integrative amyloid-tau-mitochondrial hypothesis assumes that the primary cause of AD is the neurotoxicity of A beta oligomers and tau oligomers, mitochondrial dysfunction, and their mutual synergy. For the development of new efficient AD drugs, targeting the elimination of neurotoxicity, mutual potentiation of effects, and unwanted protein interactions of risk factors and biomarkers (mainly A beta oligomers, tau oligomers, and mitochondrial dysfunction) in the early stage of the disease seems promising.
Review
Biochemistry & Molecular Biology
Pasquale Picone, Tiziana Sanfilippo, Sonya Vasto, Sara Baldassano, Rossella Guggino, Domenico Nuzzo, Donatella Bulone, Pier Luigi San Biagio, Emanuela Muscolino, Roberto Monastero, Clelia Dispenza, Daniela Giacomazza
Summary: Alzheimer's disease is the most common neurodegenerative disorder in the elderly, characterized by senile plaques and neurofibrillary tangles. There is currently a lack of treatment options aside from symptomatic medications. This review presents research results on the use of peptides of different sizes for the treatment of Alzheimer's disease.
Review
Biochemistry & Molecular Biology
Yuanxin Zhao, Buhan Liu, Jian Wang, Long Xu, Sihang Yu, Jiaying Fu, Xiaoyu Yan, Jing Su
Summary: Neuroinflammation mediated by microglia is a common feature in neurodegenerative diseases. The accumulation of Aβ and tau proteins can disrupt the metabolism of microglia, leading to neuroinflammation.
Article
Biochemistry & Molecular Biology
Rhett J. Britton, James M. Hutchison, Charles R. Sanders
Summary: In Alzheimer's disease (AD) research, the proteins of interest are amyloid precursor protein (APP) and tau, which play crucial roles in the disease mechanism. The relationship between A beta and tau pathologies remains unclear, with studies suggesting that A beta may induce or enhance tau protein formation in neurofibrillary tangles.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Jiang Chen, Anran Fan, Song Li, Yan Xiao, Yanlin Fu, Jun-Sheng Chen, Dan Zi, Ling-Hui Zeng, Jun Tan
Summary: Alzheimer's disease (AD), the most common type of dementia, is characterized by the presence of extracellular senile plaques composed of beta-amyloid peptides and intracellular neurofibrillary tangles containing phosphorylated-tau protein. This study has demonstrated the interaction between soluble tau and the N-terminal of amyloid precursor protein (APP) in vitro and in vivo, as well as the involvement of APP in the cellular uptake of tau through endocytosis. Targeting the pathological interaction between N-terminal APP and tau could be a promising therapeutic strategy for AD.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Jasvinder Singh Bhatti, Satinder Kaur, Jayapriya Mishra, Harikrishnareddy Dibbanti, Arti Singh, Arubala P. Reddy, Gurjit Kaur Bhatti, P. Hemachandra Reddy
Summary: Alzheimer's disease (AD) is a neurodegenerative disease that involves synaptic damage, mitochondrial abnormalities, microRNA deregulation, hormonal imbalance, increased astrocytes & microglia, and accumulation of amyloid & beta; and phosphorylated Tau. Targeting mitochondrial proteins, including dynamin-related protein 1 (Drp1), may be a potential therapeutic approach for preventing AD pathology.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Kseniia S. Orobets, Andrey L. Karamyshev
Summary: Alzheimer's disease is a common neurodegenerative disorder associated with age or inherited mutations. It is characterized by severe dementia that affects memory, cognitive functions, and daily life. The disease is linked to the accumulation of cytotoxic amyloid beta and hyperphosphorylated tau protein, as well as other pathological features. Various treatment options, such as antibody-based therapy and stem cell transplantation, are being investigated.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Geriatrics & Gerontology
Jinsu Park, Meenu Madan, Srinivasulu Chigurupati, Seung Hyun Baek, Yoonsuk Cho, Mohamed R. Mughal, Amin Yu, Sic L. Chan, Jogi Pattisapu, Mark P. Mattson, Dong-Gyu Jo
Summary: AQP1 levels are elevated in the cerebral cortex during the early stages of AD, particularly in vulnerable neurons, and increase as aging progresses in AD mouse models. AQP1 appears to reduce A beta production by inhibiting the binding between BACE1 and APP.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2021)
Review
Chemistry, Inorganic & Nuclear
Yunjie Xu, Hao Xiong, Bin Zhang, Injun Lee, Jianlei Xie, Mingle Li, Han Zhang, Jong Seung Kim
Summary: Alzheimer's disease is a common form of dementia that is closely related to the aggregation of Aβ and Tau proteins in the brain, resulting in memory and learning deficits. Photodynamic therapy has emerged as a promising alternative for Alzheimer's treatment by using photon-triggered reactive oxygen species to intervene in the protein aggregations. This review summarizes the principles of photodynamic therapy, the state-of-the-art photodynamic molecules/photo-nanomedicine, and the pros and cons of this therapy, while providing suggestions for overcoming challenges in this field.
COORDINATION CHEMISTRY REVIEWS
(2022)
Article
Medicine, General & Internal
Giulia Bivona, Matilda Iemmolo, Tommaso Piccoli, Luisa Agnello, Bruna Lo Sasso, Marcello Ciaccio, Giulio Ghersi
Summary: Alzheimer's disease (AD) is the most common form of cognitive decline, characterized by aggregates of A beta and tau protein. In addition to A beta deposition, inflammation and microglia activation in the brain may also play a role in the pathogenesis of AD.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Kate L. Jordan, David J. Koss, Tiago F. Outeiro, Flaviano Giorgini
Summary: This review highlights the important roles of Rab GTPases in vesicle transport and membrane trafficking, and their implications in the pathogenesis of various diseases. It also provides an overview of the current state of pharmacological targeting of Rabs and discusses the challenges of therapeutically targeting these small proteins in humans, particularly in the context of Alzheimer's disease.
Article
Cell Biology
Qi Shen, Xiaolei Wu, Zhan Zhang, Di Zhang, Sihua Yang, Da Xing
Summary: The study found that inducing gamma oscillations with non-invasive light flicker can reduce Alzheimer's disease-related pathology. By increasing the anchoring of amyloid precursor protein (APP) to the plasma membrane for non-amyloidogenic processing and interacting with KCC2, it helps maintain surface GABA(A) receptor alpha 1 levels and reduce beta-amyloid (A beta) production. These findings highlight the importance of enhancing APP trafficking to the plasma membrane in the reduction of A beta load in Alzheimer's disease.
Review
Neurosciences
Rebecca M. C. Gabriele, Emily Abel, Nick C. Fox, Selina Wray, Charles Arber
Summary: Amyloid precursor protein (APP) and its cleavage fragment Amyloid-beta (A beta) play crucial roles in Alzheimer's disease (AD). Genetic alterations that increase the overall dosage of APP or favor the generation of more aggregation-prone A beta species directly contribute to the disease. Lowering APP expression is an attractive approach for AD treatment and prevention. New technologies that reduce APP expression may offer disease modification and slow clinical progression.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Jingyi Liu, Chao Liu, Jinfeng Zhang, Yunming Zhang, Keyin Liu, Ju-Xian Song, Sravan Gopalkrishnashetty Sreenivasmurthy, Ziying Wang, Yesi Shi, Chengchao Chu, Yang Zhang, Caisheng Wu, Xianhua Deng, Xingyang Liu, Jing Song, Rongqiang Zhuang, Shugiong Huang, Pengfei Zhang, Min Li, Lei Wen, Yun Wu Zhang, Gang Liu
Article
Biochemistry & Molecular Biology
Zhouyi Rong, Baoying Cheng, Li Zhong, Xiaowen Ye, Xin Li, Lin Jia, Yanfang Li, Francis Shue, Na Wang, Yiyun Cheng, Xiaohua Huang, Chia-Chen Liu, John D. Fryer, Xin Wang, Yun-wu Zhang, Honghua Zheng
Article
Biochemistry & Molecular Biology
Dongdong Zhao, Yunqiang Zhou, Yuanhui Huo, Jian Meng, Xiaoxia Xiao, Linkun Han, Xian Zhang, Hong Luo, Dan Can, Hao Sun, Timothy Y. Huang, Xin Wang, Jie Zhang, Fa-rong Liu, Huaxi Xu, Yun-wu Zhang
Summary: In this study, RPS23RG1 was found to play a role in tauopathies by regulating the degradation of p35 and suppressing Cdk5 activation to inhibit tau hyperphosphorylation. Reduced levels of RPS23RG1 trigger aberrant Cdk5-p35 activation, leading to tau hyperphosphorylation and impaired axon outgrowth. These findings suggest that RPS23RG1 may serve as a potential therapeutic target in tauopathy disorders.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Cell Biology
Zhaoji Liu, Jinhuan Ning, Xiaoyuan Zheng, Jian Meng, Linkun Han, Honghua Zheng, Li Zhong, Xiao-Fen Chen, Xian Zhang, Hong Luo, Dan Can, Huaxi Xu, Yun-wu Zhang
CELL DEATH & DISEASE
(2020)
Article
Cell Biology
Mengxi Niu, Naizhen Zheng, Zijie Wang, Yue Gao, Xianghua Luo, Zhicai Chen, Xing Fu, Yanyan Wang, Ting Wang, Manqing Liu, Tingting Yao, Peijie Yao, Jian Meng, Yunqiang Zhou, Yunlong Ge, Zhanxiang Wang, Qilin Ma, Huaxi Xu, Yun-wu Zhang
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)
Article
Cell Biology
Yuanhui Huo, Yue Gao, Qiuyang Zheng, Dongdong Zhao, Tiantian Guo, Shuo Zhang, Yuzhe Zeng, Yiyun Cheng, Huaping Gu, Lishan Zhang, Bin Zhu, Hong Luo, Xian Zhang, Ying Zhou, Yun-wu Zhang, Hao Sun, Huaxi Xu, Xin Wang
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)
Article
Chemistry, Multidisciplinary
Yang Shen, Linbin Li, Xiaoxia Xiao, Sihan Yang, Yuhui Hua, Yinglu Wang, Yun-wu Zhang, Yandong Zhang
Summary: The study demonstrates a unique photochemical desaturation strategy for efficient synthesis of Illicium sesquiterpenes, including a 13-step gram-scale synthesis of (-)-merrilactone A using inexpensive starting materials.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Multidisciplinary Sciences
Hongfeng Zhang, Yujuan Hong, Weijie Yang, Ruimin Wang, Ting Yao, Jian Wang, Ke Liu, Huilong Yuan, Chaoqun Xu, Yuanyuan Zhou, Guanxian Li, Lishan Zhang, Hong Luo, Xian Zhang, Dan Du, Hao Sun, Qiuyang Zheng, Yun-Wu Zhang, Yingjun Zhao, Ying Zhou, Huaxi Xu, Xin Wang
Summary: Loss-of-function mutations in SNX14 lead to severe cerebellar ataxia by disrupting axonal transport and mitochondrial function, ultimately affecting Purkinje cells and causing the pathogenesis of the disease.
NATIONAL SCIENCE REVIEW
(2021)
Article
Cell Biology
Yue Wei, Menghui Ma, Sheng Lin, Xin Li, Yue Shu, Ziwei Wang, Yuhang Zhou, Banglian Hu, Baoying Cheng, Shengshun Duan, Xiaohua Huang, Huaxi Xu, Yun-Wu Zhang, Honghua Zheng
Summary: Recent research has found that shedding of CSF1R and TREM2 may play a role in neurodegenerative diseases, particularly the CSF1R I794T variant. Inhibition of shedding was shown to decrease cleaved fragments associated with the I794T variant, suggesting that the cleaved ectodomain fragment may serve as a diagnostic biomarker for ALSP.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Immunology
Baoying Cheng, Xin Li, Kai Dai, Shengshun Duan, Zhouyi Rong, Yingmin Chen, Liangcheng Lu, Zhaoji Liu, Xiaohua Huang, Huaxi Xu, Yun-Wu Zhang, Honghua Zheng
Summary: TREM2 and CSF1R interact directly in microglia cells, modulating their expression levels. Administration of CSF1 partially restores the survival ability of Trem2-deficient microglia, showing potential therapeutic intervention in TREM2 variant-bearing patients with a high risk of Alzheimer's disease.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Muxian Zhang, Yunqiang Zhou, Yiru Jiang, Zhancheng Lu, Xiaoxia Xiao, Jinhuan Ning, Hao Sun, Xian Zhang, Hong Luo, Dan Can, Jinsheng Lu, Huaxi Xu, Yun-wu Zhang
Summary: The study compared sexual dimorphism in gene expression across primary neurons, astrocytes, and microglia derived from neonatal mouse brains, revealing different levels of sexually dimorphic genes in these primary cells, with enrichment in immune-related pathways. The sexually dimorphic genes were predominantly located on the Y chromosome, and overexpression of Eif2s3y specifically affected synaptic transmission in male neurons and caused autism-like behaviors in male mice, providing new insights into sex differences in neurological disorders.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Xuan Sheng, Yunling Yao, Ruizhi Huang, Ying Xu, Yifei Zhu, Linting Chen, Lianshuai Zhang, Wanbing Wang, Rengong Zhuo, Dan Can, Che-Feng Chang, Yun-Wu Zhang, Huaxi Xu, Guojun Bu, Li Zhong, Xiao-Fen Chen
Summary: The study showed that sTREM2 fragments 41-81 and 51-81 enhanced cell viability and inflammatory responses in primary microglia; fragment 41-81 was more efficient than 51-81 in ameliorating amyloid-related pathology and is a promising candidate for AD therapy.
JOURNAL OF NEUROINFLAMMATION
(2021)
Review
Geriatrics & Gerontology
Banglian Hu, Shengshun Duan, Ziwei Wang, Xin Li, Yuhang Zhou, Xian Zhang, Yun-Wu Zhang, Huaxi Xu, Honghua Zheng
Summary: CSF1R is a key tyrosine kinase transmembrane receptor modulating microglial homeostasis, neurogenesis, and neuronal survival in the CNS. Its dysfunction is implicated in neurodegenerative disorders including ALSP and AD. Understanding the pathophysiology of CSF1R is crucial for developing targeted therapies for related neurological diseases.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Clinical Neurology
Ping Lu, Fengpeng Wang, Shuixiu Zhou, Xiaohua Huang, Hao Sun, Yun-Wu Zhang, Yi Yao, Honghua Zheng
Summary: A novel pathogenic missense mutation in the CNTNAP2 gene was found in an infant with spontaneous recurrent seizures and intellectual disability. This mutation led to changes in neuron morphology and function, causing an imbalance in excitatory and inhibitory post-synaptic currents in the neural network, potentially contributing to the occurrence of SRSs.
FRONTIERS IN NEUROLOGY
(2021)
Article
Cell Biology
Jian Meng, Linkun Han, Naizhen Zheng, Hui Xu, Zhaoji Liu, Xian Zhang, Hong Luo, Dan Can, Hao Sun, Huaxi Xu, Yun-wu Zhang
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)
