Article
Multidisciplinary Sciences
Kevin A. Murray, Carolyn J. Hu, Sarah L. Griner, Hope Pan, Jeannette T. Bowler, Romany Abskharon, Gregory M. Rosenberg, Xinyi Cheng, Paul M. Seidler, David S. Eisenberg
Summary: Neurodegenerative diseases are characterized by the accumulation of aggregated proteins, and inhibiting the formation of these aggregates is a potential therapeutic strategy. Using de novo protein design, researchers have developed a library of mini-protein inhibitors that specifically target the amyloid structures of tau, Aβ, and α Syn. These inhibitors show promising results in preventing aggregation and rescuing motor deficits in animal models of PD and AD.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
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)
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.
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)
Article
Mathematics, Applied
Huixia Li, Hongyong Zhao
Summary: This study investigates a reaction-diffusion Alzheimer's disease model with three delays, which captures the interaction among beta-amyloid deposition, pathologic tau, and neurodegeneration biomarkers. The presence of delays leads to rich dynamics in the model. The stability of equilibrium and periodic oscillation behaviors can be determined by selecting certain delays as bifurcation parameters. Numerical simulations are conducted to explore the effects of time delays, diffusion, and treatment on biomarkers. Sensitivity analysis at multiple time points suggests the need for different targeted therapies at different stages, providing valuable guidance for Alzheimer's disease treatment.
Article
Biochemistry & Molecular Biology
Fanny Eysert, Audrey Coulon, Emmanuelle Boscher, Amandine Flaig, Tiago Mendes, Sandrine Hughes, Benjamin Grenier-Boley, Xavier Hanoulle, Florie Demiautte, Charlotte Bauer, Mikael Marttinen, Mari Takalo, Philippe Amouyel, Shruti Desai, Ian Pike, Mikko Hiltunen, Frederic Checler, Melissa Farinelli, Charlotte Delay, Nicolas Malmanche, Sebastien S. Hebert, Julie Dumont, Devrim Kilinc, Jean-Charles Lambert, Julien Chapuis
Summary: Research has shown that FERMT2 plays an important regulatory role in APP metabolism, and underexpression of FERMT2 can affect axonal growth, synaptic connectivity, and long-term potentiation, which may impact the pathogenesis of Alzheimer's disease (AD).
MOLECULAR PSYCHIATRY
(2021)
Article
Neurosciences
Sofia Michopoulou, Angus Prosser, Christopher Kipps, John Dickson, Matthew Guy, Jessica Teeling
Summary: The study found that CSF inflammation markers significantly increase with tau and neurodegeneration, but not with A beta, in a mixed memory clinic cohort. Adenosine deaminase may be the best predictor of a high likelihood of AD. Functional pathway analysis demonstrated a widespread role of inflammation in neurodegeneration, explaining over 30% of variability in tau values.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
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.
Article
Biochemistry & Molecular Biology
Antonio J. Figueira, Guilherme G. Moreira, Joana Saavedra, Isabel Cardoso, Claudio M. Gomes
Summary: The hallmark of Alzheimer's disease (AD) includes the aggregation of amyloid-beta (A beta), tau, and neuroinflammation. In this study, the researchers found that S100B protein, which is upregulated in AD, can inhibit the aggregation of A beta 42, and this activity is dependent on Ca2+ binding. They also discovered that S100B exists in tetrameric form, and tetrameric S100B is more effective in inhibiting A beta 42 aggregation. These findings highlight the importance of S100B protein in regulating AD proteotoxicity.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hallie Morton, Sudhir Kshirsagar, Erika Orlov, Lloyd E. Bunquin, Neha Sawant, Lauren Boleng, Mathew George, Tanisha Basu, Bhagavathi Ramasubramanian, Jangampalli Adi Pradeepkiran, Subodh Kumar, Murali Vijayan, Arubala P. Reddy, P. Hemachandra Reddy
Summary: Alzheimer's disease is a progressive neurodegenerative disease characterized by multiple cellular changes, mitochondrial dysfunction, and brain damage, ultimately leading to cognitive impairment.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Review
Endocrinology & Metabolism
Golnaz Goodarzi, Sadra Samavarchi Tehrani, Saeed Ebrahimi Fana, Hemen Moradi-Sardareh, Ghodratollah Panahi, Mahmood Maniati, Reza Meshkani
Summary: Alzheimer's disease (AD) and Type 2 diabetes mellitus (T2DM) share common pathophysiological mechanisms. The use of anti-diabetic drugs in AD treatment has gained attention due to the interaction between the insulin pathway and AD-related proteins. Multiple studies have shown potential neuroprotective effects of various anti-diabetic drugs in AD treatment, but further research is needed to confirm these effects.
METABOLIC BRAIN DISEASE
(2023)
Review
Neurosciences
Ai Sze Wee, Thao Dinh Nhu, Kooi Yeong Khaw, Kim San Tang, Keng Yoon Yeong
Summary: Alzheimer's disease (AD) and type 2 diabetes mellitus (DM) are both age-related diseases with a significant socio-economic burden. Although their biology is well understood, the relationship between AD and type 2 DM remains unclear. Animal models have revealed shared mechanisms between the two, such as the deposition of β-amyloid peptides and the formation of neurofibrillary tangles in AD, and hyperglycemia and insulin resistance in type 2 DM. Studies suggest that improving type 2 DM may delay or prevent the development of AD, highlighting the importance of prevention and control of type 2 DM in reducing the risk of AD. Furthermore, the potential role of alpha-glucosidase inhibitors in treating AD is also explored.
CURRENT NEUROPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Javier Alvarez, Pilar Alvarez-Illera, Jaime Santo-Domingo, Rosalba I. Fonteriz, Mayte Montero
Summary: Alzheimer's disease is the leading cause of dementia, but its molecular mechanisms are still unclear. To overcome ethical limitations, animal models are used for research. The nematode Caenorhabditis elegans has proven to be an effective model for studying Alzheimer's disease, allowing for quick and cost-effective experiments.
Article
Nutrition & Dietetics
Monica Sanchez-Tapia, Alberto Mimenza-Alvarado, Lizbeth Granados-Dominguez, Adriana Flores-Lopez, Adriana Lopez-Barradas, Victor Ortiz, Claudia Perez-Cruz, Hilda Sanchez-Vidal, Julieta Hernandez-Acosta, Jose Alberto Avila-Funes, Martha Guevara-Cruz, Armando R. Tovar, Nimbe Torres
Summary: Currently, the number of individuals with mild cognitive impairment (MCI) and dementia (D) is increasing. This study investigated the role of tau protein, beta-amyloid, LPS, and curli protein in elderly individuals with MCI or D, as well as the contribution of gut microbiota. The results showed that as individuals aged, tau protein, beta-amyloid, and LPS increased significantly in serum during MCI and D. This was associated with an increase in the abundance of E. coli that synthesize the amyloid protein curli, leading to the aggregation of amyloid proteins. Rats also exhibited an increase in curli protein abundance in the brain with aging. Thus, an alteration in the gut microbiota-brain axis, characterized by an increase in curli protein and LPS, contributes to cognitive impairment and dementia through the increase in tau and beta-amyloid protein.
Article
Biochemistry & Molecular Biology
Ioanna Tsantzali, Fotini Boufidou, Eleni Sideri, Antonis Mavromatos, Myrto G. Papaioannou, Aikaterini Foska, Ioannis Tollos, Sotirios G. Paraskevas, Anastasios Bonakis, Konstantinos I. Voumvourakis, Georgios Tsivgoulis, Elisabeth Kapaki, George P. Paraskevas
Summary: Analysis of classical cerebrospinal fluid biomarkers, especially in the context of a diagnostic system like AT(N), can be a significant tool for diagnosing Alzheimer's disease accurately during a patient's lifetime. Despite atypical clinical presentations, the classical biomarker profile was consistent with Alzheimer's disease in four patients, demonstrating the potential usefulness of these biomarkers for identifying the biochemical fingerprints of the disease.
Article
Neurosciences
Zunyu Ke, Yu Zhao, Chuanling Wang, Zhiyou Cai
INTERNATIONAL JOURNAL OF NEUROSCIENCE
(2018)
Editorial Material
Cell Biology
Anindita Das, Flavio Reis, Yasuhiro Maejima, Zhiyou Cai, Jun Ren
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2017)
Article
Pharmacology & Pharmacy
Wenbo He, Chuanling Wang, Yi Chen, Yongli He, Zhiyou Cai
PHARMACOLOGICAL REPORTS
(2017)
Article
Clinical Neurology
Zhiyou Cai, Chuanling Wang, Wenbo He, Yi Chen
CURRENT ALZHEIMER RESEARCH
(2018)
Review
Neurosciences
Yongli He, Zhiyou Cai, Yangmei Chen
INTERNATIONAL JOURNAL OF NEUROSCIENCE
(2018)
Review
Neurosciences
Sinian Li, Yiming Shao, Kanglan Li, Changmei HuangFu, Wenjie Wang, Zhou Liu, Zhiyou Cai, Bin Zhao
JOURNAL OF ALZHEIMERS DISEASE
(2018)
Review
Neurosciences
Zhiyou Cai, Pei-Feng Qiao, Cheng-Qun Wan, Min Cai, Nan-Kai Zhou, Qin Li
JOURNAL OF ALZHEIMERS DISEASE
(2018)
Review
Cell Biology
Zhi-You Cai, Ming Xiao, Sohel H. Quazi, Zun-Yu Ke
NEURAL REGENERATION RESEARCH
(2018)
Review
Medicine, Research & Experimental
Z. Cai, Y. He, Y. Chen
CURRENT MOLECULAR MEDICINE
(2018)
Article
Medicine, Research & Experimental
Z. Cai, C. Wang, Y. Chen, W. He
CURRENT MOLECULAR MEDICINE
(2018)
Article
Neurosciences
Zhiyou Cai, Wenbo He, Feng-Juan Zhuang, Yan Chen
INTERNATIONAL JOURNAL OF NEUROSCIENCE
(2019)
Review
Neurosciences
Lianying Jiang, Jiafeng Wang, Zhigang Wang, Wenhui Huang, Yixia Yang, Zhiyou Cai, Keshen Li
JOURNAL OF ALZHEIMERS DISEASE
(2018)
Article
Medicine, Research & Experimental
Yu Zhao, Zunyu Ke, Wenbo He, Zhiyou Cai
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
(2019)
Article
Geriatrics & Gerontology
Zhenting Huang, Chengqun Wan, Yangyang Wang, Peifeng Qiao, Qian Zou, Jingxi Ma, Zhou Liu, Zhiyou Cai
Summary: The study demonstrates that GMOL can ameliorate cognitive impairment in normal aged SD rats by enhancing the expression of memory-related proteins, inhibiting inflammatory factors, and improving spatial learning and memory ability.
EXPERIMENTAL AGING RESEARCH
(2021)
Article
Cell Biology
Jie Wen, Yangyang Wang, Chuanling Wang, Minghao Yuan, Fei Chen, Qian Zou, Zhiyou Cai, Bin Zhao
Summary: Dietary habits contribute to the characteristics of Alzheimer's disease (AD) and cognitive impairment, partly due to the accumulation of hyperphosphorylated Tau protein. A high-fat diet damages the brain and impairs synaptic function, leading to cognitive decline. The mechanism involves decreased expression of synaptophysin and brain-derived neurotrophic factor, impaired mitophagy, and increased Tau protein phosphorylation.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2023)