Phosphorylated Amyloid-beta (Abeta) was identified in Alzheimer's disease (AD) brain. Using an anti-sense peptide approach the human cyclin-dependent kinase-1 (CDK-1) was identified as being responsible for Abeta phosphorylation. The phosphorylated Abeta peptide showed increased neurotoxicity and reduced ability to form Congo red-positive fibrils. Mutation of the serine 26 residue and inhibition of Abeta phosphorylation by the CDK-1 inhibitor olomoucine prevented Abeta toxicity, suggesting that the phosphorylated Abeta peptide represents a toxic intermediate. Cannabinoids prevented phosphorylated Abeta toxicity. The results from this study suggest that Abeta phosphorylation could play a role in AD pathology and represent a novel therapeutic target.
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http://dx.doi.org/10.1007/0-387-23226-5_20 | DOI Listing |
Mol Neurobiol
January 2025
School of Pharmacy, Nantong University, 19 Qixiu Road, Nantong, 226001, People's Republic of China.
Growing evidence suggests that plant compounds are emerging as a tremendous source for slowing the onset and progression of Alzheimer's disease (AD). Ursonic acid (UNA) is a naturally occurring pentacyclic triterpenoid with some hypoglycemic, anticancer, and antiinflammatory activities. However, the pharmacological effects of UNA on AD are still unknown.
View Article and Find Full Text PDFJ Neurol
January 2025
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Fundació de Recerca Clínic - Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Villaroel 170, 08036, Barcelona, Spain.
Plasma tau phosphorylated at threonine 181 (p-tau181) and 217 (p-tau217) have demonstrated high accuracy for Alzheimer's disease (AD) diagnosis, defined by CSF/PET amyloid beta (Aβ) positivity, but most studies have been performed in research cohorts, limiting their generalizability. We studied plasma p-tau217 and p-tau181 for CSF Aβ status discrimination in a cohort of consecutive patients attending an academic memory clinic in Spain (July 2019-June 2024). All patients had CSF AD biomarkers performed as part of their routine clinical assessment.
View Article and Find Full Text PDFCNS Neurosci Ther
January 2025
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Background: Alzheimer's disease (AD) is a debilitating neurodegenerative disorder that is difficult to predict and is typically diagnosed only after symptoms manifest. Recently, CD4 T cell-derived double-negative T (DNT) cells have shown strong immuno-regulatory properties in both in vitro and in vivo neuronal inflammation studies. However, the effectiveness of DNT cells in treating on AD are not yet fully understood.
View Article and Find Full Text PDFAdv Protein Chem Struct Biol
January 2025
Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences Hospital (NIMHANS), Institute of National Importance, Bangalore, Karnataka, India. Electronic address:
Alzheimer's disease (AD) is a prevalent neurodegenerative disease associated with dementia and neuronal impairments in brain. AD is characterized histopathologically by two hallmark lesions: abnormally phosphorylated Tau inside neurons as intracellular NFTs and extracellular accumulation of amyloid β peptide (Aβ). Furthermore, it is unable to clarify the distinction between the brief association between the development and build-up of Aβ and the commencement of illness.
View Article and Find Full Text PDFBiosci Trends
January 2025
Department of Neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, China.
Alzheimer's disease (AD), the leading cause of dementia, significantly impacts global public health, with cases expected to exceed 150 million by 2050. Late-onset Alzheimer's disease (LOAD), predominantly influenced by the APOE-ε4 allele, exhibits complex pathogenesis involving amyloid-β (Aβ) plaques, neurofibrillary tangles (NFTs), neuroinflammation, and blood-brain barrier (BBB) disruption. Proteomics has emerged as a pivotal technology in uncovering molecular mechanisms and identifying biomarkers for early diagnosis and intervention in AD.
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