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JOURNAL ARTICLE
Ke Hou, Hope Pan, Hedieh Shahpasand-Kroner, Carolyn Hu, Romany Abskharon, Paul Seidler, Marisa Mekkittikul, Melinda Balbirnie, Carter Lantz, Michael R Sawaya, Joshua L Dolinsky, Mychica Jones, Xiaohong Zuo, Joseph A Loo, Sally Frautschy, Greg Cole, David S Eisenberg
Amyloid fibrils of tau are increasingly accepted as a cause of neuronal death and brain atrophy in Alzheimer's disease (AD). Diminishing tau aggregation is a promising strategy in the search for efficacious AD therapeutics. Previously, our laboratory designed a six-residue, nonnatural amino acid inhibitor D-TLKIVW peptide (6-DP), which can prevent tau aggregation in vitro. However, it cannot block cell-to-cell transmission of tau aggregation. Here, we find D-TLKIVWC (7-DP), a d-cysteine extension of 6-DP, not only prevents tau aggregation but also fragments tau fibrils extracted from AD brains to neutralize their seeding ability and protect neuronal cells from tau-induced toxicity...
May 3, 2024: Science Advances
#2
REVIEW
Sawsan S Al-Rawi, Ahmad Hamdy Ibrahim, Heshu Jalal Ahmed, Zhikal Omar Khudhur
BACKGROUND AND OBJECTIVES: For centuries, plant seed extracts have been widely used and valued for their benefits. They have been used in food, perfumes, aromatherapy, and traditional medicine. These natural products are renowned for their therapeutic properties and are commonly used in medicinal treatments. Their significant pharmacological profiles provide an excellent hallmark for the prevention or treatment of various diseases. In this study, we comprehensively evaluated the biological and pharmacological properties of nutmeg seeds and explored their efficacy in treating various illnesses...
June 2024: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
#3
JOURNAL ARTICLE
Dayan Liu, Tao Song, Kang Na, Shudong Wang
Alzheimer's disease (AD) is a gradually advancing neurodegenerative disorder characterized by a concealed onset. Acetylcholinesterase (AChE) is an efficient hydrolase that catalyzes the hydrolysis of acetylcholine (ACh), which regulates the concentration of ACh at synapses and then terminates ACh-mediated neurotransmission. There are inhibitors to inhibit the activity of AChE currently, but its side effects are inevitable. In various application fields where Al have gained prominence, neural network-based models for molecular design have recently emerged and demonstrate encouraging outcomes...
2024: Frontiers in artificial intelligence
#4
REVIEW
Daniel Ferreira, Noémi Nogueira, Joana Guimarães, Rui Araújo
Dementia is a major public health concern due to its increasing prevalence, substantial caregiver burden, and high financial costs. Currently, the anti-dementia drugs aim only at a symptomatic effect. The subject of prescribing these drugs in advanced stages is a matter of considerable debate, with different countries making distinct recommendations. In this review article, we analyzed the evidence regarding cognitive and functional outcomes, adverse events, health-related costs, and caregiver burden in patients with advanced Alzheimer disease (AD) and mixed dementia...
2024: Porto Biomedical Journal
#5
JOURNAL ARTICLE
Wei Wang, Tingting Pan, Rui Su, Mingbin Chen, Wandi Xiong, Congjun Xu, Ling Huang
Alzheimer's disease (AD) is a neurodegenerative disease that seriously affects human health, and current treatment strategies are far from meeting clinical needs. Inspired by multi-target drug design strategies, a series of novel natural products-based melatonin-hydroxyquinoline hybrids were designed and synthesized, targeting anti-oxidation and metal-chelating at the same time. Most of the compounds showed significant oxygen radical absorbance capacity and Aβ1-42 aggregation inhibition. Moreover, the compounds possess good blood-brain barrier permeability...
2024: Frontiers in Chemistry
#6
JOURNAL ARTICLE
Masahiro Furuta, Suguru Arii, Hiroki Umeda, Ryota Matsukawa, Katsuyuki Shizu, Hironori Kaji, Shigehiro A Kawashima, Yukiko Hori, Taisuke Tomita, Youhei Sohma, Harunobu Mitsunuma, Motomu Kanai
Aberrant aggregates of amyloid-β (Aβ) and tau protein (tau), called amyloid, are related to the etiology of Alzheimer disease (AD). Reducing amyloid levels in AD patients is a potentially effective approach to the treatment of AD. The selective degradation of amyloids via small molecule-catalyzed photooxygenation in vivo is a leading approach; however, moderate catalyst activity and the side effects of scalp injury are problematic in prior studies using AD model mice. Here, leuco ethyl violet (LEV) is identified as a highly active, amyloid-selective, and blood-brain barrier (BBB)-permeable photooxygenation catalyst that circumvents all of these problems...
April 30, 2024: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
#7
JOURNAL ARTICLE
Kerem Teralı, Dilek Ozbeyli, Duygu Yiğit-Hanoğlu, Kemal Hüsnü Can Başer, Göksel Şener, Asli Aykac
INTRODUCTION: Alzheimer's disease (AD) is a neurodegenerative condition characterized by gradual loss of cognitive abilities (dementia) and is a major public health problem. Here, we aimed at investigating the effects of Rosa damascena essential oil (RDEO) on learning and memory functions in a rat model of amnesia induced by scopolamine, as well as on changes in acetylcholinesterase (AChE) activity, M1 muscarinic acetylcholine receptor (mAChR) expression, and brain-derived neurotrophic factor (BDNF) levels in the extracted brain tissues...
May 2024: Brain and Behavior
#8
JOURNAL ARTICLE
Linlin Xu, Xiaohui Wu, Shuyue Zhao, Haodong Hu, Silei Wang, Yongxin Zhang, Jiajing Chen, Xiaochen Zhang, Yu Zhao, Rujiang Ma, Fan Huang, Linqi Shi
Accumulation of pathological tau is a hallmark of Alzheimer's disease (AD), which correlates more closely with cognitive impairment than does the amyloid-β (Aβ) burden. Autophagy is a powerful process for the clearance of toxic proteins including aberrant tau. However, compromised autophagy has been demonstrated in neurodegeneration including AD and current autophagy inducers remain enormously challenging due to inability of restoring autophagy pathway and lack of targeting specificity. Here, pathogenic tau-specific autophagy based on customized nanochaperone is developed for AD treatment...
April 30, 2024: Advanced Materials
#9
JOURNAL ARTICLE
Saba Foroughi, Kahin Shahanipour, Ramesh Monajemi, Ali Mohammad Ahadi
Thymus vulgaris and Allium cepa are plants with great medicinal importance. Thymol monoterpene and quercetin, which are present in these plants, have anti-Alzheimer's and antioxidant effects. The objectives of this research were investigating the effects of these compounds on the pathogenesis and progress of Alzheimer's disease in cells modeled by formaldehyde. MTT, flow cytometry, and RT-PCR were used to investigate the toxicity, survival rate and apoptosis of the cells, and the expression level of PP2A, GSK3, NMDAR, BACE1, and APP genes, respectively...
April 28, 2024: Brain Research
#10
JOURNAL ARTICLE
Yiwei Hu, Xiaoyang Zhao, Yue Song, Jiahui Jiang, Ting Long, Mengjing Cong, Yuhua Miao, Yonghong Liu, Zhiyou Yang, Yiguang Zhu, Junfeng Wang
Fungal linear polyketides, such as α-pyrones with a 6-alkenyl chain, have been a rich source of biologically active compounds. Two new ( 1 and 2 ) and four known ( 3 - 6 ) 6-alkenylpyrone polyketides were isolated from a marine-derived strain of the fungus Arthrinium arundinis . Their structures were determined based on extensive spectroscopic analysis. The biosynthetic gene cluster ( alt ) for alternapyrones was identified from A. arundinis ZSDS-F3 and validated by heterologous expression in Aspergillus nidulans A1145 ΔSTΔEM, which revealed that the cytochrome P450 monooxygenase Alt2' could convert the methyl group 26-CH3 to a carboxyl group to produce 4 from 3 ...
April 30, 2024: Journal of Natural Products
#11
JOURNAL ARTICLE
Shuai Tao, Hongbin Hu, Liwen Kong, Zeping Lyu, Zumin Wang, Jie Zhao, Shuang Liu
Alzheimer's disease (AD) is a common and serious form of elderly dementia, but early detection and treatment of mild cognitive impairment can help slow down the progression of dementia. Recent studies have shown that there is a relationship between overall cognitive function and motor function and gait abnormalities. We recruited 302 cases from the Rehabilitation Hospital Affiliated to National Rehabilitation Aids Research Center and included 193 of them according to the screening criteria, including 137 patients with MCI and 56 healthy controls (HC)...
April 25, 2024: Sheng Wu Yi Xue Gong Cheng Xue za Zhi, Journal of Biomedical Engineering, Shengwu Yixue Gongchengxue Zazhi
#12
JOURNAL ARTICLE
Jiawei Wang, He Li, Canran Wang, Dayong Li, Yong Zhang, Meichan Shen, Xiangdong Xu, Tong Wu
BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Olfactory dysfunction (OD) is an important nonmotor feature of PD. Dl-3-n-Butylphthalide (NBP) is a synthetic compound isolated from Apium graveolens seeds. The present study was conducted to investigate the effect of NBP on olfaction in rotenone-induced Parkinson's rats to explore the mechanism and pathway of OD in PD. METHODS: The PD model was established using rotenone-induced SD rats, divided into blank control, model, and treatment groups...
2024: Frontiers in Neurology
#13
JOURNAL ARTICLE
Deepak Kumar, Govind Singh, Tarun, Meenakshi Dhanawat, Sumeet Gupta, Mohamed A Morsy, Anroop B Nair, Asmaa I Matouk
BACKGROUND: Alzheimer's disease is a neurological dysfunction of the brain caused by neurodegeneration and oxidative stress. Some viruses, such as herpes viruses, HSV-1, and HSV-2, are causative agents of Alzheimer's disease and result in β-amyloid peptide and tau protein accumulation in the brain. Some antiviral drugs, such as valacyclovir, acyclovir, and foscarnet, reduce amyloid-beta and P-tau. Pavetta indica leaves are also reported for their antiviral properties. The current study aimed to find out the significance of using Pavetta indica methanolic extract and acyclovir against Alzheimer's disease induced by streptozotocin...
April 27, 2024: Endocrine, Metabolic & Immune Disorders Drug Targets
#14
JOURNAL ARTICLE
Madia Lozupone, Vittorio Dibello, Rodolfo Sardone, Fabio Castellana, Roberta Zupo, Luisa Lampignano, Ilaria Bortone, Roberta Stallone, Mario Altamura, Antonello Bellomo, Antonio Daniele, Vincenzo Solfrizzi, Francesco Panza
INTRODUCTION: In the last decade, the efforts conducted for discovering Alzheimer's Disease (AD) treatments targeting the best-known pathogenic factors [amyloid-β (Aβ), tau protein, and neuroinflammation] were mostly unsuccessful. Given that a systemic failure of Aβ clearance was supposed to primarily contribute to AD development and progression, disease-modifying therapies with anti-Aβ monoclonal antibodies (e.g. solanezumab, bapineuzumab, gantenerumab, aducanumab, lecanemab and donanemab) are ongoing in randomized clinical trials (RCTs) with contrasting results...
April 29, 2024: Expert Opinion on Drug Discovery
#15
REVIEW
Hyun-Ju Lee, Hee-Jeong Choi, Yoo Joo Jeong, Yoon-Hee Na, Jin Tae Hong, Ji Min Han, Hyang-Sook Hoe, Key-Hwan Lim
The prevalence of Alzheimer's disease (AD) and its associated economic and societal burdens are on the rise, but there are no curative treatments for AD. Interestingly, this neurodegenerative disease shares several biological and pathophysiological features with cancer, including cell-cycle dysregulation, angiogenesis, mitochondrial dysfunction, protein misfolding, and DNA damage. However, the genetic factors contributing to the overlap in biological processes between cancer and AD have not been actively studied...
April 27, 2024: International Journal of Biological Macromolecules
#16
JOURNAL ARTICLE
Hyun-Ju Lee, JinHan Nam, Jeong-Woo Hwang, Jin-Hee Park, Yoo Joo Jeong, Ji-Yeong Jang, Su-Jeong Kim, A-Ran Jo, Hyang-Sook Hoe
Dopamine plays important roles in cognitive function and inflammation and therefore is involved in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). Drugs that increase or maintain dopamine levels in the brain could be a therapeutic strategy for AD. However, the effects of dopamine and its precursor levodopa (L-DOPA) on Aβ/tau pathology in vivo and the underlying molecular mechanisms have not been studied in detail. Here, we investigated whether L-DOPA treatment alters neuroinflammation, Aβ pathology, and tau phosphorylation in 5xFAD mice, a model of AD...
April 30, 2024: Molecular Brain
#17
JOURNAL ARTICLE
Olivia Wagemann, Haiyan Liu, Guoqiao Wang, Xinyu Shi, Tobias Bittner, Marzia A Scelsi, Martin R Farlow, David B Clifford, Charlene Supnet-Bell, Anna M Santacruz, Andrew J Aschenbrenner, Jason J Hassenstab, Tammie L S Benzinger, Brian A Gordon, Kelley A Coalier, Carlos Cruchaga, Laura Ibanez, Richard J Perrin, Chengjie Xiong, Yan Li, John C Morris, James J Lah, Sarah B Berman, Erik D Roberson, Christopher H van Dyck, Douglas Galasko, Serge Gauthier, Ging-Yuek R Hsiung, William S Brooks, Jérémie Pariente, Catherine J Mummery, Gregory S Day, John M Ringman, Patricio Chrem Mendez, Peter St George-Hyslop, Nick C Fox, Kazushi Suzuki, Hamid R Okhravi, Jasmeer Chhatwal, Johannes Levin, Mathias Jucker, John R Sims, Karen C Holdridge, Nicholas K Proctor, Roy Yaari, Scott W Andersen, Michele Mancini, Jorge Llibre-Guerra, Randall J Bateman, Eric McDade
IMPORTANCE: Effects of antiamyloid agents, targeting either fibrillar or soluble monomeric amyloid peptides, on downstream biomarkers in cerebrospinal fluid (CSF) and plasma are largely unknown in dominantly inherited Alzheimer disease (DIAD). OBJECTIVE: To investigate longitudinal biomarker changes of synaptic dysfunction, neuroinflammation, and neurodegeneration in individuals with DIAD who are receiving antiamyloid treatment. DESIGN, SETTING, AND PARTICIPANTS: From 2012 to 2019, the Dominantly Inherited Alzheimer Network Trial Unit (DIAN-TU-001) study, a double-blind, placebo-controlled, randomized clinical trial, investigated gantenerumab and solanezumab in DIAD...
April 29, 2024: JAMA Neurology
#18
JOURNAL ARTICLE
Nissi Sharon, Vinod G Ugale, Pannala Padmaja, Deepak Lokwani, Chandradeep Salunkhe, Padmaja Shete, Pedavenkatagari Narayana Reddy, Prasad P Kulkarni
Alzheimer's disease (AD) is a neurodegenerative disease affecting mental ability and neurocognitive functions. Cholinesterase enzymes affect concentration of acetylcholine in the brain, leading to dementia. Thus, there is an urgent need to develop novel dual cholinesterase inhibitors as possible anti-AD drugs. Herein, we have designed and synthesized a novel series of 9H-carbazole-4H-chromenes 4(a-l) through a one-pot three-component reaction of salicylaldehydes (1), hydroxycarbazole (2) and N-methyl-1-(methylthio)-2-nitroethenamine (3) using triethylamine as a catalyst in ethanol...
April 29, 2024: Molecular Diversity
#19
JOURNAL ARTICLE
Xiao-Hong Hu, Kai-Yue Yu, Xin-Xin Li, Jin-Nan Zhang, Juan-Juan Jiao, Zhao-Jun Wang, Hong-Yan Cai, Lei Wang, Ye-Xin He, Mei-Na Wu
The orexin system is closely related to the pathogenesis of Alzheimer's disease (AD). Orexin-A aggravates cognitive dysfunction and increases amyloid β (Aβ) deposition in AD model mice, but studies of different dual orexin receptor (OXR) antagonists in AD have shown inconsistent results. Our previous study revealed that OX1R blockade aggravates cognitive deficits and pathological progression in 3xTg-AD mice, but the effects of OX2R and its potential mechanism in AD have not been reported. In the present study, OX2R was blocked by oral administration of the selective OX2R antagonist MK-1064, and the effects of OX2R blockade on cognitive dysfunction and neuropsychiatric symptoms in 3xTg-AD mice were evaluated via behavioral tests...
April 29, 2024: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
#20
REVIEW
You-Yue Li, Dan-Dan Guo, Ruo-Nan Duan, Yi Li
Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder characterized by aberrant amyloid precursor protein (APP) cleavage, pathological aggregations of beta-amyloid (Aβ) that make up Aβ plaques and hyperphosphorylation of Tau that makes up neurofibrillary tangles (NFTs). Although progress has been made in research on AD, the fundamental causes of this disease have not been fully elucidated. Recent studies have shown that vascular dysfunction especially the loss of pericytes plays a significant role in the onset of AD...
April 2, 2024: Frontiers in Bioscience (Landmark Edition)
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