AI Article Synopsis
- Alzheimer's disease (AD) is characterized by harmful amyloid plaques and tau protein tangles; tau hyperphosphorylation plays a major role in its pathology.
- Hypothermia is an effective method for testing potential neuroprotective compounds that could reduce tau issues in AD.
- The study found that substances like palm11-PrRP31 and liraglutide can decrease tau hyperphosphorylation in specific neuronal cultures, indicating their potential as treatments for neurodegenerative diseases.
Article Abstract
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases, characterized by the accumulation of extracellular amyloid plaques and intraneuronal neurofibrillary tangles. These tangles mainly consist of hyperphosphorylated tau protein. As it induces tau hyperphosphorylation in vitro and in vivo, hypothermia is a useful tool for screening potential neuroprotective compounds that ameliorate tau pathology. In this study, we examined the effect of prolactin-releasing peptide (PrRP), its lipidized analog palm11-PrRP31 and glucagon-like-peptide-1 agonist liraglutide, substances with anorexigenic and antidiabetic properties, on tau phosphorylation and on the main kinases and phosphatases involved in AD development. Our study was conducted in a neuroblastoma cell line SH-SY5Y and rat primary neuronal cultures under normothermic and hypothermic conditions. Hypothermia induced a significant increase in tau phosphorylation at the pThr212 and pSer396/pSer404 epitopes. The palmitoylated analogs liraglutide and palm11-PrRP31 attenuated tau hyperphosphorylation, suggesting their potential use in the treatment of neurodegenerative diseases.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.3233/JAD-180837 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Spatial proteomic differences in chronic traumatic encephalopathy, Alzheimer's disease, and primary age-related tauopathy hippocampi.
Alzheimers Dement
December 2024
Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Introduction: Alzheimer's disease (AD), primary age-related tauopathy (PART), and chronic traumatic encephalopathy (CTE) all feature hyperphosphorylated tau (p-tau)-immunoreactive neurofibrillary degeneration, but differ in neuroanatomical distribution and progression of neurofibrillary degeneration and amyloid beta (Aβ) deposition.
Methods: We used Nanostring GeoMx Digital Spatial Profiling to compare the expression of 70 proteins in neurofibrillary tangle (NFT)-bearing and non-NFT-bearing neurons in hippocampal CA1, CA2, and CA4 subregions and entorhinal cortex of cases with autopsy-confirmed AD (n = 8), PART (n = 7), and CTE (n = 5).
Results: There were numerous subregion-specific differences related to Aβ processing, autophagy/proteostasis, inflammation, gliosis, oxidative stress, neuronal/synaptic integrity, and p-tau epitopes among these different disorders.
Fuzhisan ameliorates cognitive ability in Alzheimer's disease by p62 and related autophagy regulatory pathways.
Brain Res
December 2024
Department of Traditional Chinese Medicine, The First Affiliated Hospital of Shandong First Medical University (The Shandong Province Qianfoshan Hospital), Jinan 250014, PR China. Electronic address:
Background: Maintaining autophagic homeostasis has been proved to play an important role in Alzheimer's disease.
Object: The aim of this study was to investigate the effect of Fuzhisan(FZS) on autophagic function in Alzheimer's disease and to elucidate its potential mechanism through the P62 regulatory pathways.
Methods: FZS was extracted by water extraction-rotary evaporation method.
Discovery of novel bicyclic and tricyclic cyclohepta[b]thiophene derivatives as multipotent AChE and BChE inhibitors, in-Vivo and in-Vitro assays, ADMET and molecular docking simulation.
Eur J Med Chem
December 2024
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sinai University, Kantara Branch, Ismailia, 41636, Egypt.
Alzheimer's disease (AD) is primarily caused by oxidative stress, hyperphosphorylated τ-protein aggregation, and amyloid-β deposition. Changes in dopaminergic and serotoninergic neurotransmitter pathways are linked to certain symptoms of AD. Derivatives of bicyclic and tricyclic cyclohepta[b]thiophene were developed to identify new potential candidates as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors for the treatment of AD.
View Article and Find Full Text PDFDeoxyvasicinone hybrids in the management of Alzheimer's disease: Recent advances on manmade derivatives, pharmacological activities, and structure-activity relationship.
Arch Pharm (Weinheim)
January 2025
Department of Pharmacognosy, University Institute of Pharma Sciences, Chandigarh University, Mohali, Punjab, India.
Alzheimer's disease (AD) is a prevalent neurological illness that affects over 80% of aged adults globally in cases of dementia. Although the exact pathophysiological causes of AD remain unclear, its pathogenesis is primarily driven by several distinct biochemical alterations: (i) the accumulation of toxic Aβ plaques, (ii) the hyperphosphorylation of tau proteins, (iii) oxidative stress resulting in cell death, and (iv) an imbalance between the two main neurotransmitters, glutamate and acetylcholine (ACh). Currently, there are very few medications available and no treatment.
View Article and Find Full Text PDFCathepsin B Modulates Alzheimer's Disease Pathology Through SAPK/JNK Signals Following Administration of Porphyromonas gingivalis-Derived Outer Membrane Vesicles.
J Clin Periodontol
December 2024
Department of Periodontics, Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University, Shenyang, China.
Aim: Porphyromonas gingivalis, a consensus periodontal pathogen, is thought to be involved in Alzheimer's disease (AD) progression, and P. gingivalis-derived outer membrane vesicles (PgOMVs) are a key toxic factor in inducing AD pathology. This study aimed to clarify the regulatory mechanism underlying the PgOMV-induced AD-like phenotype.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!