P1-421: The role of advanced glycation endproduct (AGE) receptors in the pathogenesis of Alzheimer's disease

Increasing evidence suggests that the small EF-hand calcium-binding protein S100B plays an important role in Alzheimer's disease. Among other evidences are the increased levels of both S100B and its receptor, the Receptor for Advanced Glycation Endproducts (RAGEs) in the AD diseased brain. The regulation of RAGE signaling by S100B is complex and probably involves other ligands including the amyloid beta peptide (A), the Advanced Glycation Endproducts (AGEs), or transtheyretin. In this paper we discuss the current literature regarding the role of S100B/RAGE activation in Alzheimer's disease.

Download Full-text

Rage Isoforms, its Ligands and their Role in Pathophysiology of Alzheimer’s Disease

Current Alzheimer Research ◽

10.2174/1567205018666210218164246 ◽

2021 ◽

Vol 18 ◽

Author(s):

Rani Cathrine Chellappa ◽

Rani Palanisamy ◽

Karthikeyan Swaminathan

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Pathological Process ◽

Material Structure ◽

Multiple Forms ◽

Advanced Glycation ◽

Ligand Interaction ◽

The Brain ◽

Aβ Production

: Receptor for Advanced Glycation End product (RAGE) plays a crucial role in a variety of physiological and pathological processes due to its ability to bind a broad repertory of ligands. There are also multiple forms of RAGE that exist; some work on promoting feed-forward pathways while others perform inhibitory actions. This review focuses on the RAGE isoforms expression, its intracellular pathways activation via RAGE- ligand interaction, and its importance in the physiological and pathological process of the brain. Many studies have suggested that RAGE induces the pathophysiological changes in Alzheimer’s disease (AD) by being an intermediator of inflammation and inducer of oxidative stress. The critical roles played by RAGE in AD include its involvement in amyloid-beta (Aβ) production, clearance, synaptic impairment, and neuronal circuit dysfunction. RAGE-Aβ interaction also mediates the bi-directional crosstalk between peripheral and central systems. This interaction underlies a potential molecular pathway that disrupts the material structure and physiology of the brain. This review highlights the structure-function relation for RAGE- Aβ interaction and the role of RAGE as a potential target in the development of treatments for AD.

Download Full-text

Role of Methylglyoxal in Alzheimer’s Disease

BioMed Research International ◽

10.1155/2014/238485 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 65

Author(s):

Cristina Angeloni ◽

Laura Zambonin ◽

Silvana Hrelia

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Disorder ◽

Advanced Glycation ◽

Hyperphosphorylated Tau Protein ◽

Glycation End Products ◽

And Oxidative Stress ◽

Endogenous Process

Alzheimer’s disease is the most common and lethal neurodegenerative disorder. The major hallmarks of Alzheimer’s disease are extracellular aggregation of amyloidβpeptides and, the presence of intracellular neurofibrillary tangles formed by precipitation/aggregation of hyperphosphorylated tau protein. The etiology of Alzheimer’s disease is multifactorial and a full understanding of its pathogenesis remains elusive. Some years ago, it has been suggested that glycation may contribute to both extensive protein cross-linking and oxidative stress in Alzheimer’s disease. Glycation is an endogenous process that leads to the production of a class of compounds known as advanced glycation end products (AGEs). Interestingly, increased levels of AGEs have been observed in brains of Alzheimer’s disease patients. Methylglyoxal, a reactive intermediate of cellular metabolism, is the most potent precursor of AGEs and is strictly correlated with an increase of oxidative stress in Alzheimer’s disease. Many studies are showing that methylglyoxal and methylglyoxal-derived AGEs play a key role in the etiopathogenesis of Alzheimer's disease.

Download Full-text

The role of abnormal mitochondrial dynamics in the pathogenesis of Alzheimer's disease

Yearbook of Neurology and Neurosurgery ◽

10.1016/s0513-5117(09)79132-x ◽

2009 ◽

Vol 2009 ◽

pp. 149-150

Author(s):

J.P. Blass

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mitochondrial Dynamics

Download Full-text

Dissecting the role of Corticotropin-releasing hormone receptor type 1 in Alzheimer's Disease

Pharmacopsychiatry ◽

10.1055/s-0031-1292513 ◽

2011 ◽

Vol 44 (06) ◽

Author(s):

K Lerche ◽

M Willem ◽

K Kleinknecht ◽

C Romberg ◽

U Konietzko ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Hormone Receptor ◽

Receptor Type ◽

Corticotropin Releasing Hormone ◽

Releasing Hormone

Download Full-text

Role of melatonin in regulating neurogenesis: Implications for the neurodegenerative pathology and analogous therapeutics for Alzheimer’s disease

Melatonin Research ◽

10.32794/mr11250059 ◽

2020 ◽

Vol 3 (2) ◽

pp. 216-242 ◽

Cited By ~ 1

Author(s):

Mayuri Shukla ◽

Areechun Sotthibundhu ◽

Piyarat Govitrapong

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Adult Neurogenesis ◽

Adult Brain ◽

Therapeutic Approaches ◽

Therapeutic Implications ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Progenitor Cell Proliferation

The revelation of adult brain exhibiting neurogenesis has established that the brain possesses great plasticity and that neurons could be spawned in the neurogenic zones where hippocampal adult neurogenesis attributes to learning and memory processes. With strong implications in brain functional homeostasis, aging and cognition, various aspects of adult neurogenesis reveal exuberant mechanistic associations thereby further aiding in facilitating the therapeutic approaches regarding the development of neurodegenerative processes in Alzheimer’s Disease (AD). Impaired neurogenesis has been significantly evident in AD with compromised hippocampal function and cognitive deficits. Melatonin the pineal indolamine augments neurogenesis and has been linked to AD development as its levels are compromised with disease progression. Here, in this review, we discuss and appraise the mechanisms via which melatonin regulates neurogenesis in pathophysiological conditions which would unravel the molecular basis in such conditions and its role in endogenous brain repair. Also, its components as key regulators of neural stem and progenitor cell proliferation and differentiation in the embryonic and adult brain would aid in accentuating the therapeutic implications of this indoleamine in line of prevention and treatment of AD.

Download Full-text