scholarly journals Copper, Iron, Selenium and Lipo-Glycemic Dysmetabolism in Alzheimer’s Disease

2021 ◽  
Vol 22 (17) ◽  
pp. 9461
Author(s):  
Jan Aaseth ◽  
Anatoly V. Skalny ◽  
Per M. Roos ◽  
Jan Alexander ◽  
Michael Aschner ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Wide Spectrum ◽  
Protein Glycation ◽  
Special Focus ◽  
Fenton Chemistry ◽  
Glycation End Products ◽  
Aβ Generation ◽  
Rage Expression

The aim of the present review is to discuss traditional hypotheses on the etiopathogenesis of Alzheimer’s disease (AD), as well as the role of metabolic-syndrome-related mechanisms in AD development with a special focus on advanced glycation end-products (AGEs) and their role in metal-induced neurodegeneration in AD. Persistent hyperglycemia along with oxidative stress results in increased protein glycation and formation of AGEs. The latter were shown to possess a wide spectrum of neurotoxic effects including increased Aβ generation and aggregation. In addition, AGE binding to receptor for AGE (RAGE) induces a variety of pathways contributing to neuroinflammation. The existing data also demonstrate that AGE toxicity seems to mediate the involvement of copper (Cu) and potentially other metals in AD pathogenesis. Specifically, Cu promotes AGE formation, AGE-Aβ cross-linking and up-regulation of RAGE expression. Moreover, Aβ glycation was shown to increase prooxidant effects of Cu through Fenton chemistry. Given the role of AGE and RAGE, as well as metal toxicity in AD pathogenesis, it is proposed that metal chelation and/or incretins may slow down oxidative damage. In addition, selenium (Se) compounds seem to attenuate the intracellular toxicity of the deranged tau and Aβ, as well as inhibiting AGE accumulation and metal-induced neurotoxicity.

scholarly journals The Complexity of Sporadic Alzheimer’s Disease Pathogenesis: The Role of RAGE as Therapeutic Target to Promote Neuroprotection by Inhibiting Neurovascular Dysfunction

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Lorena Perrone ◽  
Oualid Sbai ◽  
Peter P. Nawroth ◽  
Angelika Bierhaus
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Current Knowledge ◽  
Amyloid Peptide ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Glycation End Products ◽  
Cellular Dysfunction ◽  
Neurovascular Dysfunction

Alzheimer's disease (AD) is the most common cause of dementia. Amyloid plaques and neurofibrillary tangles are prominent pathological features of AD. Aging and age-dependent oxidative stress are the major nongenetic risk factors for AD. The beta-amyloid peptide (Aβ), the major component of plaques, and advanced glycation end products (AGEs) are key activators of plaque-associated cellular dysfunction. Aβ and AGEs bind to the receptor for AGEs (RAGE), which transmits the signal from RAGE via redox-sensitive pathways to nuclear factor kappa-B (NF-κB). RAGE-mediated signaling is an important contributor to neurodegeneration in AD. We will summarize the current knowledge and ongoing studies on RAGE function in AD. We will also present evidence for a novel pathway induced by RAGE in AD, which leads to the expression of thioredoxin interacting protein (TXNIP), providing further evidence that pharmacological inhibition of RAGE will promote neuroprotection by blocking neurovascular dysfunction in AD.

scholarly journals Nutrition and AGE-ing: Focusing on Alzheimer’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Giulia Abate ◽  
Mariagrazia Marziano ◽  
Wiramon Rungratanawanich ◽  
Maurizio Memo ◽  
Daniela Uberti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Saturated Fatty Acids ◽  
The Elderly ◽  
Cooking Methods ◽  
Chronic Disability ◽  
Modifiable Factors ◽  
Glycation End Products ◽  
Food And Nutrition

Recently, the role of food and nutrition in preventing or delaying chronic disability in the elderly population has received great attention. Thanks to their ability to influence biochemical and biological processes, bioactive nutrients are considered modifiable factors capable of preserving a healthy brain status. A diet rich in vitamins and polyphenols and poor in saturated fatty acids has been recommended. In the prospective of a healthy diet, cooking methods should be also considered. In fact, cooking procedures can modify the original dietary content, contributing not only to the loss of healthy nutrients, but also to the formation of toxins, including advanced glycation end products (AGEs). These harmful compounds are adsorbed at intestinal levels and can contribute to the ageing process. The accumulation of AGEs in ageing (“AGE-ing”) is further involved in the exacerbation of neurodegenerative and many other chronic diseases. In this review, we discuss food’s dual role as both source of bioactive nutrients and reservoir for potential toxic compounds—paying particular attention to the importance of proper nutrition in preventing/delaying Alzheimer’s disease. In addition, we focus on the importance of a good education in processing food in order to benefit from the nutritional properties of an optimal diet.

scholarly journals The Role of PGC1α in Alzheimer’s Disease and Therapeutic Interventions

2021 ◽  
Vol 22 (11) ◽  
pp. 5769
Author(s):  
Bibiana C. Mota ◽  
Magdalena Sastre
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Amyloid Β ◽  
Therapeutic Interventions ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Aβ Generation ◽  
Therapy Studies

The peroxisome proliferator-activated receptor co-activator-1α (PGC1α) belongs to a family of transcriptional regulators, which act as co-activators for a number of transcription factors, including PPARs, NRFs, oestrogen receptors, etc. PGC1α has been implicated in the control of mitochondrial biogenesis, the regulation of the synthesis of ROS and inflammatory cytokines, as well as genes controlling metabolic processes. The levels of PGC1α have been shown to be altered in neurodegenerative disorders. In the brains of Alzheimer’s disease (AD) patients and animal models of amyloidosis, PGC1α expression was reduced compared with healthy individuals. Recently, it was shown that overexpression of PGC1α resulted in reduced amyloid-β (Aβ) generation, particularly by regulating the expression of BACE1, the rate-limiting enzyme involved in the production of Aβ. These results provide evidence pointing toward PGC1α activation as a new therapeutic avenue for AD, which has been supported by the promising observations of treatments with drugs that enhance the expression of PGC1α and gene therapy studies in animal models of AD. This review summarizes the different ways and mechanisms whereby PGC1α can be neuroprotective in AD and the pre-clinical treatments that have been explored so far.

scholarly journals Role of Methylglyoxal in Alzheimer’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
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.

scholarly journals The Potential Role of Cytokines and Growth Factors in the Pathogenesis of Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2790
Author(s):  
Gilbert Ogunmokun ◽  
Saikat Dewanjee ◽  
Pratik Chakraborty ◽  
Chandrasekhar Valupadas ◽  
Anupama Chaudhary ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Growth Factors ◽  
Microglial Activation ◽  
Potential Role ◽  
Neuronal Function ◽  
Glycation End Products ◽  
Gradual Decay ◽  
Shed Light

Alzheimer’s disease (AD) is one of the most prominent neurodegenerative diseases, which impairs cognitive function in afflicted individuals. AD results in gradual decay of neuronal function as a consequence of diverse degenerating events. Several neuroimmune players (such as cytokines and growth factors that are key players in maintaining CNS homeostasis) turn aberrant during crosstalk between the innate and adaptive immunities. This aberrance underlies neuroinflammation and drives neuronal cells toward apoptotic decline. Neuroinflammation involves microglial activation and has been shown to exacerbate AD. This review attempted to elucidate the role of cytokines, growth factors, and associated mechanisms implicated in the course of AD, especially with neuroinflammation. We also evaluated the propensities and specific mechanism(s) of cytokines and growth factors impacting neuron upon apoptotic decline and further shed light on the availability and accessibility of cytokines across the blood-brain barrier and choroid plexus in AD pathophysiology. The pathogenic and the protective roles of macrophage migration and inhibitory factors, neurotrophic factors, hematopoietic-related growth factors, TAU phosphorylation, advanced glycation end products, complement system, and glial cells in AD and neuropsychiatric pathology were also discussed. Taken together, the emerging roles of these factors in AD pathology emphasize the importance of building novel strategies for an effective therapeutic/neuropsychiatric management of AD in clinics.

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

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

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

2020 ◽  
Vol 3 (2) ◽  
pp. 216-242 ◽  
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.   

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