Article
Clinical Neurology
Christina M. Moloney, Sydney A. Labuzan, Julia E. Crook, Habeeba Siddiqui, Monica Castanedes-Casey, Christian Lachner, Ronald C. Petersen, Ranjan Duara, Neill R. Graff-Radford, Dennis W. Dickson, Michelle M. Mielke, Melissa E. Murray
Summary: This study aims to characterize the recognition of phosphorylated tau sites in early neurofibrillary tangle maturity levels, which may explain why these fluid biomarkers can be observed before symptom onset.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Yalun Zhang, Yi Zhang, Yahyah Aman, Cheung Toa Ng, Wing-Hin Chau, Zhigang Zhang, Ming Yue, Christopher Bohm, Yizhen Jia, Siwen Li, Qiuju Yuan, Jennifer Griffin, Kin Chiu, Dana S. M. Wong, Binbin Wang, Dongyan Jin, Ekaterina Rogaeva, Paul E. Fraser, Evandro F. Fang, Peter St George-Hyslop, You-Qiang Song
Summary: Research has shown that the transcription factor PAX6 is increased in Alzheimer's disease, playing a key role in the hyperphosphorylation of tau protein induced by amyloid-beta. Downregulation of PAX6 can protect against amyloid-beta-induced neuronal death. This study provides novel potential targets for pharmaceutical intervention by modulating signaling pathways involving CDK/pRB/E2F1.
Article
Clinical Neurology
Binita Rajbanshi, Anuj Guruacharya, James W. Mandell, George S. Bloom
Summary: Tau phosphorylation at T217 increases as Alzheimer's disease progresses and is associated with diseased neurons. Extracellular tau oligomers can induce an increase in tau(pT217). Phosphorylation reduces tau's affinity for microtubules.
ALZHEIMERS & DEMENTIA
(2023)
Article
Neurosciences
Alejandra Martinez-Maldonado, Miguel Angel Ontiveros-Torres, Charles R. Harrington, Jose Francisco Montiel-Sosa, Raul Garcia-Tapia Prandiz, Patricia Bocanegra-Lopez, Andrew Michael Sorsby-Vargas, Marely Bravo-Munoz, Benjamin Floran-Garduno, Ignacio Villanueva-Fierro, George Perry, Linda Garces-Ramirez, Fidel de la Cruz, Sandra Martinez-Robles, Mar Pacheco-Herrero, Jose Luna-Munoz
Summary: This study evaluated and compared the processing of pathological tau in PSP and AD. Results showed that phosphorylated tau was as abundant in PSP as in AD, but there were differences in the truncated tau species, indicating the potential presence of truncated tau species different from those observed in AD in PSP.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Clinical Neurology
Thais Rafael Guimaraes, Eric Swanson, Julia Kofler, Amantha Thathiah
Summary: The study identifies a link between G protein-coupled receptor kinases (GRKs) and the pathological phosphorylation and accumulation of tau in Alzheimer's disease (AD), as well as a novel role in regulating the disease's pathological hallmarks. The expression patterns of different GRKs vary in AD patients compared to control subjects, indicating potential involvement in tau phosphorylation and NFT formation.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Review
Immunology
Minghui Wang, Hu Zhang, Jiling Liang, Jielun Huang, Ning Chen
Summary: Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by the formation of neurofibrillary tangles and senile plaques. Neuroinflammation, specifically the long-term activation of pro-inflammatory microglia and NLRP3 inflammasomes, plays a crucial role in the development and progression of AD. Exercise has been found to ameliorate AD by regulating the immune response and promoting neurogenesis in the hippocampus.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Neurosciences
Esther M. Blessing, Ankit Parekh, Rebecca A. Betensky, James Babb, Natalie Saba, Ludovic Debure, Andrew W. Varga, Indu Ayappa, David M. Rapoport, Tracy A. Butler, Mony J. de Leon, Thomas Wisniewski, Brian J. Lopresti, Ricardo S. Osorio
Summary: This study found that lower body temperature is associated with increased tau pathology in cognitively normal older adults, suggesting that temperature may play an important role in the development of Alzheimer's disease.
NEUROBIOLOGY OF DISEASE
(2022)
Review
Chemistry, Medicinal
Kundlik Gadhave, Deepak Kumar, Vladimir N. Uversky, Rajanish Giri
Summary: The exact molecular mechanisms associated with Alzheimer's disease remain a mystery, making the utilization of signaling pathways as potential drug targets limited. It is necessary to find correlations and cross-talk between these pathways and establish different therapeutic targets for a better understanding of the biological events responsible for AD-related neurodegeneration. Consideration should be given to the central role of autophagy in AD and its interplay with other pathways as the finest therapeutic strategy.
MEDICINAL RESEARCH REVIEWS
(2021)
Review
Medicine, Research & Experimental
Bradley Hyman
Summary: Alzheimer's disease is a debilitating disease characterized by the presence of neurofibrillary tangles and senile plaques in the brain. The aggregation of tau protein in the tangles and amyloid β proteins in the plaques has been extensively studied. It has now been established that smaller, oligomeric forms of amyloid β can also be bioactive. This review explores the possibility that soluble, nonfibrillar, bioactive forms of tau may be a dominant driver of neurodegeneration in AD.
ANNUAL REVIEW OF MEDICINE
(2023)
Review
Pharmacology & Pharmacy
Zhikun Shi, Hongyu Chen, Xu Zhou, Wei Yang, Yang Lin
Summary: Ginsenosides, the most important pharmacological active ingredient of ginseng, have shown potential in inhibiting the pathogenesis of AD. This review analyzes the mechanisms of ginsenosides in inhibiting the deposition of Aβ and NFTs, as well as their neuroprotective effects through antioxidant, anti-inflammatory, and anti-apoptosis mechanisms. Furthermore, the delivery route and mode of ginsenosides are discussed, providing a deeper understanding of their clinical application in AD treatment.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Majedul Islam, Fengyun Shen, Deepika Regmi, Deguo Du
Summary: Tauopathies are neurodegenerative diseases characterized by abnormal tau deposition in the brain. Currently, there are no approved disease-modifying therapies for tauopathies. Drug repurposing offers a potential alternative approach to discover effective drugs for treating these diseases.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Neurosciences
Zuha Waheed, Jawaria Choudhary, Faria Hasan Jatala, Aneeqa Noor, Inga Zerr, Saima Zafar
Summary: Tau is a microtubule-associated binding protein in the nervous system that stabilizes microtubules in nerve cells. It accumulates as aggregates and tangles, leading to various pathologies. Different splice variants of tau are expressed in the brain and contribute to neurodegenerative diseases. The isoforms have different roles and undergo post-translational modifications at different rates, affecting their physiological and pathological attributes. This article aims to review the roles of tau isoforms and their underlying mechanisms in neurological deficits.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Andrea Gonzalez, Sandeep Kumar Singh, Macarena Churruca, Ricardo B. Maccioni
Summary: Alzheimer's disease is a neurodegenerative disease characterized by progressive cognitive impairment, apathy, and neuropsychiatric disorders. The main pathological features are tau oligomers and Aβ plaques. Protein kinases and phosphatases play a role in the hyperphosphorylation of tau and its self-assembly.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Ujala Sehar, Priyanka Rawat, Arubala P. Reddy, Jonathan Kopel, P. Hemachandra Reddy
Summary: Alzheimer's disease is a progressive neurodegenerative disease that affects behavior, thinking, and memory in elderly individuals. It can occur in two forms – early onset familial and late-onset sporadic, with genetic mutations and lifestyle/environment factors playing a role in its development. Key pathological changes include the production and accumulation of Aβ and p-tau in affected brain regions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Neurosciences
Tomas Kavanagh, Aditi Halder, Eleanor Drummond
Summary: Pathological tau aggregation is a key feature of many neurodegenerative diseases, but varies widely in affected brain regions, symptoms, morphology, conformation, and isoform ratio. Tau interactome studies provide important insights into disease mechanisms and cellular environment during tau aggregation. Analysis of 12 tau interactome studies revealed consistent interactions with proteins involved in RNA binding, ribosome, and proteasome function, with differences observed between human and rodent studies. Dysregulation of tau interactions was observed during the development of pathology, suggesting a role for RNA binding proteins in driving tau pathology.
MOLECULAR NEURODEGENERATION
(2022)