P-glycoprotein (ABCB1) and Oxidative Stress: Focus on Alzheimer’s Disease

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/7905486 ◽

2017 ◽

Vol 2017 ◽

pp. 1-13 ◽

Cited By ~ 16

Author(s):

Giulia Sita ◽

Patrizia Hrelia ◽

Andrea Tarozzi ◽

Fabiana Morroni

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Therapeutic Drug ◽

Amyloid A ◽

P Glycoprotein ◽

And Function ◽

The Brain ◽

Brain Homeostasis

ATP-binding cassette (ABC) transporters, in particular P-glycoprotein (encoded by ABCB1), are important and selective elements of the blood-brain barrier (BBB), and they actively contribute to brain homeostasis. Changes in ABCB1 expression and/or function at the BBB may not only alter the expression and function of other molecules at the BBB but also affect brain environment. Over the last decade, a number of reports have shown that ABCB1 actively mediates the transport of beta amyloid (Aβ) peptide. This finding has opened up an entirely new line of research in the field of Alzheimer’s disease (AD). Indeed, despite intense research efforts, AD remains an unsolved pathology and effective therapies are still unavailable. Here, we review the crucial role of ABCB1 in the Aβtransport and how oxidative stress may interfere with this process. A detailed understanding of ABCB1 regulation can provide the basis for improved neuroprotection in AD and also enhanced therapeutic drug delivery to the brain.

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Sex Differences and the Influence of Sex Hormones on Cognition through Adulthood and the Aging Process

Brain Sciences ◽

10.3390/brainsci8090163 ◽

2018 ◽

Vol 8 (9) ◽

pp. 163 ◽

Cited By ~ 17

Author(s):

Caroline Gurvich ◽

Kate Hoy ◽

Natalie Thomas ◽

Jayashri Kulkarni

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Sex Differences ◽

Cognitive Functioning ◽

Sex Hormones ◽

Reproductive Function ◽

Health And Disease ◽

And Function ◽

The Brain

Hormones of the hypothalamic-pituitary-gonadal (HPG) axis that regulate reproductive function have multiple effects on the development, maintenance and function of the brain. Sex differences in cognitive functioning have been reported in both health and disease, which may be partly attributed to sex hormones. The aim of the current paper was to provide a theoretical review of how sex hormones influence cognitive functioning across the lifespan as well as provide an overview of the literature on sex differences and the role of sex hormones in cognitive decline, specifically in relation to Alzheimer’s disease (AD). A summary of current hormone and sex-based interventions for enhancing cognitive functioning and/or reducing the risk of Alzheimer’s disease is also provided.

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Mitochondrial Dysfunction as a Causative Factor in Alzheimer’s Disease-Spectrum Disorders: Lymphocytes as a Window to the Brain

Current Alzheimer Research ◽

10.2174/1567205018666211208141512 ◽

2021 ◽

Vol 18 ◽

Author(s):

Marko Jörg ◽

Johanna E. Plehn ◽

Kristina Friedland ◽

Walter E. Müller

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mitochondrial Dysfunction ◽

Late Onset ◽

Causative Factor ◽

Disease Spectrum ◽

The Brain ◽

Peripheral Markers

: Alzheimer's disease (AD) is the most common progressive neurodegenerative disease. Today, AD affects millions of people worldwide and the number of AD cases will further increase with longer life expectancy. The AD brain is marked by severe neurodegeneration, such as the loss of synapses and neurons, atrophy and depletion of neurotransmitter systems, especially in the hip- pocampus and cerebral cortex. Recent findings highlight the important role of mitochondrial dys- function and increased oxidative stress in the pathophysiology of late-onset Alzheimer’s disease (LOAD). These alterations are not only observed in the brain of AD patients but also in the periph- ery. In this review, we discuss the potential role of elevated apoptosis, increased oxidative stress and mitochondrial dysfunction as peripheral markers for the detection of AD in blood cells e.g. lymphocytes. We evaluate recent findings regarding impaired mitochondrial function comprising mitochondrial respiration, reduced complex activities of the respiratory chain and altered Mitochon- drial Membrane Potential (MMP) in lymphocytes as well as in neurons. Finally, we will question whether these mitochondrial parameters might be suitable as an early peripheral marker for the de- tection of LOAD but also for the transitional stage between normal aging and Dementia, “Mild Cognitive Impairment” (MCI).

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Mitochondria, Cognitive Impairment, and Alzheimer's Disease

International Journal of Alzheimer s Disease ◽

10.4061/2009/951548 ◽

2009 ◽

Vol 2009 ◽

pp. 1-8 ◽

Cited By ~ 22

Author(s):

M. Mancuso ◽

V. Calsolaro ◽

D. Orsucci ◽

C. Carlesi ◽

A. Choub ◽

...

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mtdna Haplogroups ◽

Mtdna Damage ◽

Amyloid A ◽

Model Of Alzheimer’S Disease ◽

Biochemical Genetic ◽

Energy Failure

To date, the beta amyloid (Aβ) cascade hypothesis remains the main pathogenetic model of Alzheimer's disease (AD), but its role in the majority of sporadic AD cases is unclear. The “mitochondrial cascade hypothesis” could explain many of the biochemical, genetic, and pathological features of sporadic AD. Somatic mutations in mitochondrial DNA (mtDNA) could cause energy failure, increased oxidative stress, and accumulation of Aβ, which in a vicious cycle reinforce the mtDNA damage and the oxidative stress. Despite the evidence of mitochondrial dysfunction in AD, no causative mutations in the mtDNA have been detected so far. Indeed, results of studies on the role of mtDNA haplogroups in AD are controversial. In this review we discuss the role of the mitochondria, and especially of the mtDNA, in the cascade of events leading to neurodegeneration, dementia, and AD.

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The role of metabolic syndrome in Alzheimer’s disease

10.5327/1516-3180.319 ◽

2021 ◽

Author(s):

Gláucia Maria Senhorinha ◽

Arlys Emanuel Mendes da Silva Santos ◽

Douglas Daniel Dophine

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Insulin Resistance ◽

Alzheimer's Disease ◽

Metabolic Syndrome ◽

Brain Regions ◽

Alzheimer Dementia ◽

The Metabolic Syndrome ◽

The Brain

Background: Metabolic syndrome (MS) leads to the deposits formation of insoluble protein aggregates, neuroinflammation, oxidative stress, neuronal insulin resistance, progressive insulin resistance, desensitization and β-amyloid amyloidosis in the brain, besides direct ischemic effects which are closely associated with Alzheimer’s disease (AD).1 Objectives: The present study seeks to understand the role of the metabolic syndrome in the pathophysiology of Alzheimer’s disease and to describe preventive and therapeutic interventions. Methods: PUBMED and Web of Science were the databases used, the following descriptors were used to search the articles: “Alzheimer Disease” OR “Alzheimer Dementia” AND “Metabolic Syndrome”. Results: The studies in general have shown that MS is related to AD through brain insulin resistance, triggered by oxidative stress and neuroinflammation. It is related to the progressive atrophy of brain regions involved in the progression of AD. Insulin resistance in the brain is related to the progressive atrophy of the brain regions from initial progression of AD. These regions are cingulate cortices, medial temporal lobe, prefrontal gyri and other regions.³ Thus, there is an inhibition of the mechanisms of beta-amyloid removal, leading to its accumulation, which generates neuroinflammation, that in turn potentiates insulin resistance in the central nervous system, contributing to the genesis and progression of cognitive damage.2,3 Conclusions: Insulin resistance plays a major role in the initiation and perpetuation of cognitive impairment in AD. Furthermore, the components of the MS associated with AD, when treated with preventive and therapeutic measures, break this association by promoting rebalancing of the metabolism.

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The Role of Irisin in Alzheimer’s Disease

Journal of Clinical Medicine ◽

10.3390/jcm7110407 ◽

2018 ◽

Vol 7 (11) ◽

pp. 407 ◽

Cited By ~ 9

Author(s):

Oh Kim ◽

Juhyun Song

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Genetic Background ◽

Senile Plaques ◽

Metabolic Dysfunction ◽

Lipid Imbalance ◽

The Relationship ◽

The Brain

Alzheimer’s disease (AD) is characterized by progressive memory dysfunction, oxidative stress, and presence of senile plaques formed by amyloid beta (A β ) accumulation in the brain. AD is one of the most important causes of morbidity and mortality worldwide. AD has a variety of risk factors, including environmental factors, metabolic dysfunction, and genetic background. Recent research has highlighted the relationship between AD and systemic metabolic changes such as glucose and lipid imbalance and insulin resistance. Irisin, a myokine closely linked to exercise, has been associated with glucose metabolism, insulin sensitivity, and fat browning. Recent studies have suggested that irisin is involved in the process in central nervous system (CNS) such as neurogenesis and has reported the effects of irisin on AD as one of the neurodegenerative disease. Here, we review the roles of irisin with respect to AD and suggest that irisin highlight therapeutic important roles in AD. Thus, we propose that irisin could be a potential future target for ameliorating AD pathology and preventing AD onset.

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The role of neuropeptide somatostatin in the brain and its application in treating neurological disorders

Experimental & Molecular Medicine ◽

10.1038/s12276-021-00580-4 ◽

2021 ◽

Author(s):

You-Hyang Song ◽

Jiwon Yoon ◽

Seung-Hee Lee

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurological Disorders ◽

Current Knowledge ◽

Cortical Circuits ◽

Protein Marker ◽

And Function ◽

Novel Drug ◽

The Brain

AbstractSomatostatin (SST) is a well-known neuropeptide that is expressed throughout the brain. In the cortex, SST is expressed in a subset of GABAergic neurons and is known as a protein marker of inhibitory interneurons. Recent studies have identified the key functions of SST in modulating cortical circuits in the brain and cognitive function. Furthermore, reduced expression of SST is a hallmark of various neurological disorders, including Alzheimer’s disease and depression. In this review, we summarize the current knowledge on SST expression and function in the brain. In particular, we describe the physiological roles of SST-positive interneurons in the cortex. We further describe the causal relationship between pathophysiological changes in SST function and various neurological disorders, such as Alzheimer’s disease. Finally, we discuss potential treatments and possibility of novel drug developments for neurological disorders based on the current knowledge on the function of SST and SST analogs in the brain derived from experimental and clinical studies.

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Chronic Stress and Oxidative Stress as Common Factors of the Pathogenesis of Depression and Alzheimer’s Disease: The Role of Antioxidants in Prevention and Treatment

Antioxidants ◽

10.3390/antiox10091439 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1439 ◽

Cited By ~ 1

Author(s):

Gabriela Juszczyk ◽

Joanna Mikulska ◽

Kamila Kasperek ◽

Diana Pietrzak ◽

Weronika Mrozek ◽

...

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Vitamin E ◽

Chronic Stress ◽

Antioxidant Properties ◽

Stress Oxidative ◽

The Relationship ◽

The Brain

There is a growing body of scientific research showing the link between depression and dementia in Alzheimer’s disease (AD). The chronic stress contributes to the formation of oxidative stress in the parts of the brain involved in the development of depression and AD. The scientific literature reports the significant role of antioxidants, which are highly effective in treating these diseases. In this review, we have summarized the relationship between chronic stress, oxidative stress, and the changes in the brain they cause occurring in the brain. Among all the compounds showing antioxidant properties, the most promising results in AD treatment were observed for Vitamin E, coenzyme Q10 (CoQ10), melatonin, polyphenols, curcumin, and selenium. In case of depression treatment, the greatest potential was observed in curcumin, zinc, selenium, vitamin E, and saffron.

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Beta-Amyloid Downregulates MDR1-P-Glycoprotein (Abcb1) Expression at the Blood-Brain Barrier in Mice

International Journal of Alzheimer s Disease ◽

10.4061/2011/690121 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 24

Author(s):

Anja Brenn ◽

Markus Grube ◽

Michele Peters ◽

Andrea Fischer ◽

Gabriele Jedlitschky ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Amyloid Angiopathy ◽

Amyloid A ◽

P Glycoprotein ◽

Blood Brain ◽

Age Related ◽

The Brain

Neurovascular dysfunction is an important component of Alzheimer's disease, leading to reduced clearance across the blood-brain barrier and accumulation of neurotoxicβ-amyloid (Aβ) peptides in the brain. It has been shown that the ABC transport protein P-glycoprotein (P-gp, ABCB1) is involved in the export of Aβfrom the brain into the blood. To determine whether Aβinfluences the expression of key Aβtransporters, we studied the effects of 1-day subcutaneous Aβ1-40 and Aβ1-42 administration via Alzet mini-osmotic pumps on P-gp, BCRP, LRP1, and RAGE expression in the brain of 90-day-old male FVB mice. Our results demonstrate significantly reduced P-gp, LRP1, and RAGE mRNA expression in mice treated with Aβ1-42 compared to controls, while BCRP expression was not affected. The expression of the four proteins was unchanged in mice treated with Aβ1-40 or reverse-sequence peptides. These findings indicate that, in addition to the age-related decrease of P-gp expression, Aβ1-42 itself downregulates the expression of P-gp and other Aβ-transporters, which could exacerbate the intracerebral accumulation of Aβand thereby accelerate neurodegeneration in Alzheimer's disease and cerebralβ-amyloid angiopathy.

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