Receptor for Advanced Glycation End Products: Dementia and Cognitive Impairment

Abstract

The pathophysiological processes of dementia and cognitive impairment are linked to advanced glycation end products (AGEs) and their receptor (RAGE).The neurofibrillary tangles (NFTs) of abnormally hyperphosphorylated tau protein and senile plaques (SPs), which are brought on by amyloid beta (Aβ) deposition, are the hallmarks of Alzheimer’s disease (AD), a progressive neurodegenerative condition. Advanced glycation end products that are produced as a result of vascular dysfunction are bound by the receptor for advanced glycation end products (RAGE). Dementia and cognitive impairment could develop when RAGE binds to Aβ and produces reactive oxygen species, aggravating Aβ buildup and ultimately resulting in SPs and NFTs. RAGE could be a more powerful biomarker than Aβ because it is implicated in early AD. The resident immune cells in the brain known as microglia are essential for healthy brain function. Microglia is prominent in the amyloid plaques’ outside border as well as their central region in Alzheimer’s disease. Microglial cells, in the opinion of some authors, actively contribute to the formation of amyloid plaques. In this review, we first discuss the early diagnosis of dementia and cognitive impairment, and then detail the interaction between RAGE and Aβ and Tau that is necessary to cause dementia and cognitive impairment pathology, and it is anticipated that the creation of RAGE probes will help in the diagnosis and treatment of dementia and cognitive impairment.

Targeting Abnormal Tau Phosphorylation for Alzheimer’s Therapeutics

“…Caspases 2 and 3 cleave the C-terminus at Asp314 and Asp421, respectively, while caspase 6 cleaves the N-terminus. In addition to affecting microtubule binding and aggregation, cleaving the C-terminal of tau has been linked to mitochondrial and synaptic damage [46][47][48][49][50]. However, it is important to note that not all post-translational modifications (PTMs) contribute to the acceleration of tau pathology and Alzheimer's disease (AD) progression.…”

“…Another tau PTM, dityrosine (DiY) cross-links, is induced by oxidative stress and has been observed on human AD-derived tau oligomers and PHFs. Interestingly, DiY cross-links can facilitate the formation of non-toxic, soluble tau oligomers, inhibit the formation of β-sheets and further extension of prefibrils, and increase the insolubility and stability of tau fibrils in AD [51][52][53][54].…”

Silver Nanoparticles From Cassia alata L. Incorporated to Coconut Oil‐Oleogel Based Ointment As An Alternative for Diabetes Mellitus Wound Healing: Optimization, In Vitro and In Vivo Tests

“…The oleogel formulation with a concentration of 4.5 % Na-CMC and 12.5 % beeswax, with the addition of AgNPs, resulted in a semi-solid preparation with the scent of coconut oil and a pH of 5, deemed safe for human skin application. [47] The test results for oil-binding capacity and spreading power were obtained at 99.83 % and 4.6 cm, respectively. Organoleptic and homogeneity tests indicated that the oleogel ointment preparation is homogeneous and stable, showing no changes in physical properties.…”

Ferroptosis Signaling Pathways: Alzheimer's Disease

“…The main protein that stores iron is called ferritin, and brain iron levels may be reflected in CSF ferritin levels. In particular in individuals with high A-deposition or APOE-4 carriers, studies have indicated that CSF ferritin can be recognised as a possible biomarker, which is better to predict disease progression and future cognitive impairment [14]. Moreover, a high likelihood of brain hypometabolism and cognitive impairment is indicated by high CSF ferritin levels.…”