scholarly journals Putative Involvement of Endocrine Disruptors in the Alzheimer's disease Via the Insulin-Regulated Aminopeptidase / GLUT4 Pathway

2020 ◽  
Vol 18 ◽  
Author(s):  
María Jesús Ramírez-Expósito ◽  
Jose Manuel Martínez-Martos ◽  
Vanesa Cantón-Habas ◽  
María del Pilar Carrera González
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Surface ◽  
Glucose Transporter ◽  
Cell Function ◽  
Sensory Information ◽  
Inhibitory Effect ◽  
Pharmacological Intervention ◽  
Pancreatic Cell ◽  
The One

: It has been well established that there is a connection between type II diabetes (DMTII) and Alzheimer's disease (AD). In fact, the increase in AD incidence may be an emerging complication of DMTII. Both pathologies are related to estradiol (E2) exposure; on the one hand, estrogen receptors (ER) are emerging as important modulators of glucose homeostasis through ß-pancreatic cell function; on the other hand, brain bioenergetic and cognitive deficits have been related to the down regulation of brain ERs, contributing to women ageing and AD susceptibility, both related to the reduction in estradiol levels and the deficits in brain metabolism. Here we discuss that environmental contaminants with estrogenic capacity such as bisphenol A (BPA) could develop pharmacological effects similar to those of E2, which could affect ß-pancreatic cell function by increasing the biosynthesis of glucose-induced insulin after extranuclear ER binding. BPA-induced hyperinsulinemia would promote the translocation of glucose transporter 4 (GLUT4) which is located next to insulin-regulated aminopeptidase (IRAP) in intracellular vesicles. In insulin-responsive tissues, IRAP and GLUT 4 are routed together to the cell surface after insulin stimulation. IRAP is also the angiotensin IV (AngIV) receptor, and AngIV associates the brain reninangiotensin system (bRAS) with AD, since AngIV is related to learning, memory, emotional responses, and processing of sensory information not only through its inhibitory effect on IRAP but also through the stimulation of glucose uptake by increasing the presence of IRAP/GLUT4 at the cell surface. Thus, the IRAP/GLUT4 pathway is an emerging target for the pharmacological intervention against AD.

Lighting and Alzheimer’s disease and related dementias: Spotlight on sleep and depression

2021 ◽  
Vol 53 (5) ◽  
pp. 405-422
Author(s):  
MG Figueiro ◽  
HC Kales
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disease ◽  
Sleep Disturbances ◽  
Well Being ◽  
Pharmacological Intervention ◽  
Negative Effects ◽  
Health And Well Being ◽  
Positive Results

Alzheimer’s disease and related dementias is the collective term for a progressive neurodegenerative disease for which there is presently no cure. This paper focuses on two symptoms of the disease, sleep disturbances and depression, and discusses how light can be used as a non-pharmacological intervention to mitigate their negative effects. Bright days and dark nights are needed for health and well-being, but the present components of the built environment, especially those places where older adults spend most of their days, are too dimly illuminated during the day and too bright at night. To be effective light needs to be correctly specified, implemented and measured. Yet, without the appropriate specification and measurement of the stimulus, researchers will not be able to successfully demonstrate positive results in the field, nor will lighting designers and specifiers have the confidence to implement lighting solutions for promoting better sleep and mood in this population.

A ratiometric electrochemical strategy for sensitive determination of Furin activity based on dual signal amplification and antifouling nanosurfaces

The Analyst ◽  
2017 ◽  
Vol 142 (22) ◽  
pp. 4215-4220 ◽  
Author(s):  
Dazhi Yao ◽  
Wenqi Zhao ◽  
Limin Zhang ◽  
Yang Tian
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Surface ◽  
Signal Amplification ◽  
Accurate Method ◽  
Sensitive Determination ◽  
Dual Signal Amplification

Developing a sensitive and accurate method for Furin activity is still the bottleneck for understanding the role played by Furin in cell-surface systems and even in Alzheimer's disease.

scholarly journals Chenodeoxycholic Acid Ameliorates AlCl3-Induced Alzheimer’s Disease Neurotoxicity and Cognitive Deterioration via Enhanced Insulin Signaling in Rats

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1992 ◽  
Author(s):  
Firas H. Bazzari ◽  
Dalaal M. Abdallah ◽  
Hanan S. El-Abhar
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Chenodeoxycholic Acid ◽  
Insulin Signaling ◽  
Glucose Transporter ◽  
Farnesoid X Receptor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Significant Difference

Insulin resistance is a major risk factor for Alzheimer’s disease (AD). Chenodeoxycholic acid (CDCA) and synthetic Farnesoid X receptor (FXR) ligands have shown promising outcomes in ameliorating insulin resistance associated with various medical conditions. This study aimed to investigate whether CDCA treatment has any potential in AD management through improving insulin signaling. Adult male Wistar rats were randomly allocated into three groups and treated for six consecutive weeks; control (vehicle), AD-model (AlCl3 50 mg/kg/day i.p) and CDCA-treated group (AlCl3 + CDCA 90 mg/kg/day p.o from day 15). CDCA improved cognition as assessed by Morris Water Maze and Y-maze tests and preserved normal histological features. Moreover, CDCA lowered hippocampal beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and amyloid-beta 42 (Aβ42). Although no significant difference was observed in hippocampal insulin level, CDCA reduced insulin receptor substrate-1 phosphorylation at serine-307 (pSer307-IRS1), while increased protein kinase B (Akt) activation, glucose transporter type 4 (GLUT4), peroxisome proliferator-activated receptor gamma (PPARγ) and glucagon-like peptide-1 (GLP-1). Additionally, CDCA activated cAMP response element-binding protein (CREB) and enhanced brain-derived neurotrophic factor (BDNF). Ultimately, CDCA was able to improve insulin sensitivity in the hippocampi of AlCl3-treated rats, which highlights its potential in AD management.

Aging-dependent changes of glial cell function and Alzheimer’s disease

2015 ◽  
Vol 357 ◽  
pp. e511
Author(s):  
R. von Bernhardi ◽  
F. Cornejo ◽  
L. Eugenín-von Bernhardi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glial Cell ◽  
Cell Function

scholarly journals Conversational System as Assistant Tool in Reminiscence Therapy for People with Early-Stage of Alzheimer’s

Healthcare ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1036
Author(s):  
Victor Morales-de-Jesús ◽  
Helena Gómez-Adorno ◽  
María Somodevilla-García ◽  
Darnes Vilariño
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Life History ◽  
Patient Information ◽  
Early Stage ◽  
Care Center ◽  
Pharmacological Intervention ◽  
Emotional States ◽  
Reminiscence Therapy ◽  
Past Experiences

Reminiscence therapy is a non-pharmacological intervention that helps mitigate unstable psychological and emotional states in patients with Alzheimer’s disease, where past experiences are evoked through conversations between the patients and their caregivers, stimulating autobiographical episodic memory. It is highly recommended that people with Alzheimer regularly receive this type of therapy. In this paper, we describe the development of a conversational system that can be used as a tool to provide reminiscence therapy to people with Alzheimer’s disease. The system has the ability to personalize the therapy according to the patients information related to their preferences, life history and lifestyle. An evaluation conducted with eleven people related to patient care (caregiver = 9, geriatric doctor = 1, care center assistant = 1) shows that the system is capable of carrying out a reminiscence therapy according to the patient information in a successful manner.

scholarly journals The Alzheimer's gene SORL1 is a key regulator of endosomal recycling in human neurons

2021 ◽  
Author(s):  
Swati Mishra ◽  
Allison Knupp ◽  
Marcell Szabo ◽  
Chizuru Kinoshita ◽  
Dale W. Hailey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Surface ◽  
Induced Pluripotent Stem Cell ◽  
Endosomal Trafficking ◽  
Altered Expression ◽  
Therapeutic Implications ◽  
Endosomal Recycling ◽  
Human Neurons ◽  
Early Endosomes

Background: Loss of the Sortilin-related receptor 1 (SORL1) gene seems to act as a causal event for Alzheimer's disease (AD). Recent studies have established that loss of SORL1, as well as mutations in autosomal dominant AD genes APP and PSEN1/2, pathogenically converge by swelling early endosomes, AD's cytopathological hallmark. Acting together with the retromer trafficking complex, SORL1 has been shown to regulate the recycling of the amyloid precursor protein (APP) out of the endosome, contributing to endosomal swelling and to APP misprocessing. We hypothesized that SORL1 plays a broader role in neuronal endosomal recycling and used human induced pluripotent stem cell derived neurons (hiPSC-Ns) to test this hypothesis. We examined endosomal recycling of three transmembrane proteins linked to AD pathophysiology: APP, the BDNF receptor Tropomyosin-related kinase B (TRKB), and the glutamate receptor subunit AMPA1 (GLUA1). Methods: We used isogenic hiPSCs engineered to have SORL1 depleted or to have enhanced SORL1 expression. We differentiated neurons from these cell lines and mapped the trafficking of APP, TRKB and GLUA1 within the endosomal network using confocal microscopy. We also performed cell surface recycling and lysosomal degradation assays to assess the functionality of the endosomal network. Finally, we analyzed alterations in gene expression in SORL1 depleted neurons using RNA-sequencing. Results: We find that as with APP, endosomal trafficking of GLUA1 and TRKB is impaired by loss of SORL1. Conversely, increased SORL1 expression enhances endosomal recycling for APP and GLUA1. Our unbiased transcriptomic data further support SORL1's role in endosomal recycling. We observe altered expression networks that regulate cell surface trafficking and neurotrophic signaling Conclusion: Collectively, and together with other recent observations, these findings suggest that SORL1 is a key and broad regulator of retromer-dependent endosomal recycling in neurons, a conclusion that has both pathogenic and therapeutic implications for Alzheimer's disease.

The management of dementia

2012 ◽  
pp. 411-419
Author(s):  
John-Paul Taylor ◽  
Simon Fleminger
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Intellectual Disability ◽  
Clinical Syndrome ◽  
Older Age ◽  
Age Group ◽  
Cerebral Damage ◽  
Memory Problems ◽  
The One

The term dementia is used in two different ways. First there are the dementias. These are diseases that cause progressive and diffuse cerebral damage, of which Alzheimer's disease is the most common. Second, dementia can be used to refer to a clinical syndrome. Thus dementia is ‘an acquired global impairment of intellect, memory, and personality, but without impairment of consciousness’. For clinicians this is the preferred usage, and the one adopted in this chapter. It demands that the cause of the dementia is explored, and makes no comment on the likely prognosis. This chapter will focus on the management of dementia regardless of the cause; however given the burden of dementia in older age, the discussion will be invariably, but not exclusively, slanted towards the management of dementia in this age group. Aspects of management specific to individual diseases which produce dementia will be avoided. In addition, a discourse on the management of cognitive and memory problems is excluded as these are described elsewhere (see Chapters 2.5.4 and 6.2.7). Patients who suffer the dementia before 18 years of age will, by and large, not be included; their needs are often best met by services provided for people with intellectual disability.

scholarly journals The inhibition of cellular toxicity of amyloid-β by dissociated transthyretin

2020 ◽  
Vol 295 (41) ◽  
pp. 14015-14024 ◽  
Author(s):  
Qin Cao ◽  
Daniel H. Anderson ◽  
Wilson Y. Liang ◽  
Joshua Chou ◽  
Lorena Saelices
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protective Effect ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
Aβ Oligomers ◽  
Cellular Toxicity ◽  
Computational Docking

The protective effect of transthyretin (TTR) on cellular toxicity of β-amyloid (Aβ) has been previously reported. TTR is a tetrameric carrier of thyroxine in blood and cerebrospinal fluid, the pathogenic aggregation of which causes systemic amyloidosis. However, studies have documented a protective effect of TTR against cellular toxicity of pathogenic Aβ, a protein associated with Alzheimer's disease. TTR binds Aβ, alters its aggregation, and inhibits its toxicity both in vitro and in vivo. In this study, we investigate whether the amyloidogenic ability of TTR and its antiamyloid inhibitory effect are associated. Using protein aggregation and cytotoxicity assays, we found that the dissociation of the TTR tetramer, required for its amyloid pathogenesis, is also necessary to prevent cellular toxicity from Aβ oligomers. These findings suggest that the Aβ-binding site of TTR may be hidden in its tetrameric form. Aided by computational docking and peptide screening, we identified a TTR segment that is capable of altering Aβ aggregation and toxicity, mimicking TTR cellular protection. EM, immune detection analysis, and assessment of aggregation and cytotoxicity revealed that the TTR segment inhibits Aβ oligomer formation and also promotes the formation of nontoxic, nonamyloid amorphous aggregates, which are more sensitive to protease digestion. Finally, this segment also inhibits seeding of Aβ catalyzed by Aβ fibrils extracted from the brain of an Alzheimer's patient. Together, these findings suggest that mimicking the inhibitory effect of TTR with peptide-based therapeutics represents an additional avenue to explore for the treatment of Alzheimer's disease.

Fiat Lux: The Light Became Therapy. An Overview on the Bright Light Therapy in Alzheimer’s Disease Sleep Disorders

2020 ◽  
Vol 77 (1) ◽  
pp. 113-125 ◽  
Author(s):  
Ilaria Roccaro ◽  
Daniela Smirni
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sleep Disorders ◽  
Visual Information ◽  
Bright Light ◽  
Light Therapy ◽  
Pharmacological Intervention ◽  
Biological Clocks ◽  
Bright Light Therapy ◽  
Effective Response

Background: A system of photosensitive retinal ganglion cells provides ‘non-visual’ information on the circadian sequences of light to the suprachiasmatic nucleus (SCN), which, as the ‘master clock’, synchronizes the chronobiological mechanisms of all the biological clocks. Damage to SCN structure alters circadian behavioral and hormonal rhythms and interferes with a regular sleep-wake pattern. Several studies have shown that, in aging and in Alzheimer’s disease (AD), circadian rhythms change their synchronization with the environment and behavior loses sync with light. Objective: The current overview aims to examine research studies showing the effect of bright light therapy (BLT) on sleep disorders and sleep-wake patterns in AD. Methods: A literature search was conducted, taking into consideration the relevant studies over the last 20 years. Fifteen studies have been thorough: seven followed an environmental-architectural approach and eight followed a treatment devices approach. Results: Studies agree in considering BLT as a promising non-pharmacological intervention to compensate for circadian rhythm alterations and they support the need for standardized protocols that allow a comparison between multicenter studies. Conclusion: Interestingly, in an attempt to contain the spread of the COVID-19 pandemic, health authorities have forced the population to stay home. Therefore, AD people are not currently able to enjoy exposure to sunlight. It is predictable that they may experience an exacerbation of circadian disturbances and that the BLT can be an effective response to prevent such exacerbation.

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