Neurofibrillary tangles (NFTs) are one of the pathological hallmarks of Alzheimer's disease (AD) and are primarily composed of aggregates of hyperphosphorylated forms of the microtubule associated protein tau. It is likely that an imbalance of kinase and phosphatase activities leads to the abnormal phosphorylation of tau and subsequent aggregation. The wide ranging therapeutic approaches that are being developed include to inhibit tau kinases, to enhance phosphatase activity, to promote microtubule stability, and to reduce tau aggregate formation and/or enhance their clearance with small molecule drugs or by immunotherapeutic means. Most of these promising approaches are still in preclinical development whilst some have progressed to Phase II clinical trials. By pursuing these lines of study, a viable therapy for AD and related tauopathies may be obtained.
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http://dx.doi.org/10.2174/156720511796717195 | DOI Listing |
JCI Insight
January 2025
Dianne Hoppes Nunnally Laboratory Research Division, Joslin Diabetes Center, Boston, United States of America.
Background: We aimed to characterize factors associated with the under-studied complication of cognitive decline in aging people with long-duration type 1 diabetes (T1D).
Methods: Joslin "Medalists" (n = 222; T1D ≥ 50 years) underwent cognitive testing. Medalists (n = 52) and age-matched non-diabetic controls (n = 20) underwent neuro- and retinal imaging.
Inflammopharmacology
January 2025
Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β plaques and tau tangles, leading to cognitive decline and dementia. Insulin-like Growth Factor-1 (IGF-1) is similar in structure to insulin and is crucial for cell growth, differentiation, and regulating oxidative stress, synaptic plasticity, and mitochondrial function. IGF-1 exerts its physiological effects by binding to the IGF-1 receptor (IGF-1R) and activating PI3K/Akt pathway.
View Article and Find Full Text PDFACS Chem Neurosci
January 2025
Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
The deposition of amyloid-β (Aβ) aggregates and metal ions within senile plaques is a hallmark of Alzheimer's disease (AD). Among the modifications observed in Aβ peptides, -terminal truncation at Phe4, yielding Aβ, is highly prevalent in AD-affected brains and significantly alters Aβ's metal-binding and aggregation profiles. Despite the abundance of Zn(II) in senile plaques, its impact on the aggregation and toxicity of Aβ remains unexplored.
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2025
Key Laboratory of the Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
The single-luminophore-based ratiometric electrochemiluminescence (ECL) sensor coupling bidirectional regulator has become a research hotspot in the detection field because of its simplicity and accuracy. However, the limited bidirectional regulator hinders its further development. In this study, by leveraging the robust predictive capabilities of machine learning, we prepared an Fe-based metal-organic framework (FeMOF) as a bidirectional regulator for modulating the dual-emission ECL signals of a single luminophore for the first time.
View Article and Find Full Text PDFCent Nerv Syst Agents Med Chem
January 2025
International Center of Neuroscience and Genomic Medicine, EuroEspes Biomedical Research Center, Corunna, Spain.
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