scholarly journals Dissecting Sex-Related Cognition between Alzheimer’s Disease and Diabetes: From Molecular Mechanisms to Potential Therapeutic Strategies

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Ghulam Md Ashraf ◽  
Mahmoud Ahmed Ebada ◽  
Mohd Suhail ◽  
Ashraf Ali ◽  
Md. Sahab Uddin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Sexually Dimorphic ◽  
Metabolic Complications ◽  
Male And Female ◽  
Precise Diagnosis ◽  
Protective Strategies ◽  
The Brain

The brain is a sexually dimorphic organ that implies different functions and structures depending on sex. Current pharmacological approaches against different neurological diseases act distinctly in male and female brains. In all neurodegenerative diseases, including Alzheimer’s disease (AD), sex-related outcomes regarding pathogenesis, prevalence, and response to treatments indicate that sex differences are important for precise diagnosis and therapeutic strategy. Pathogenesis of AD includes vascular dementia, and in most cases, this is accompanied by metabolic complications with similar features as those assembled in diabetes. This review discusses how AD-associated dementia and diabetes affect cognition in relation to sex difference, as both diseases share similar pathological mechanisms. We highlight potential protective strategies to mitigate amyloid-beta (Aβ) pathogenesis, emphasizing how these drugs act in the male and female brains.

scholarly journals Magnetic Nanoparticles as In Vivo Tracers for Alzheimer’s Disease

2020 ◽  
Vol 6 (1) ◽  
pp. 13
Author(s):  
Bhargy Sharma ◽  
Konstantin Pervushin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Contrast Agents ◽  
Neurological Diseases ◽  
Pulse Sequences ◽  
Experimental Conditions ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

Drug formulations and suitable methods for their detection play a very crucial role in the development of therapeutics towards degenerative neurological diseases. For diseases such as Alzheimer’s disease, magnetic resonance imaging (MRI) is a non-invasive clinical technique suitable for early diagnosis. In this review, we will discuss the different experimental conditions which can push MRI as the technique of choice and the gold standard for early diagnosis of Alzheimer’s disease. Here, we describe and compare various techniques for administration of nanoparticles targeted to the brain and suitable formulations of nanoparticles for use as magnetically active therapeutic probes in drug delivery targeting the brain. We explore different physiological pathways involved in the transport of such nanoparticles for successful entry in the brain. In our lab, we have used different formulations of iron oxide nanoparticles (IONPs) and protein nanocages as contrast agents in anatomical MRI of an Alzheimer’s disease (AD) brain. We compare these coatings and their benefits to provide the best contrast in addition to biocompatibility properties to be used as sustainable drug-release systems. In the later sections, the contrast enhancement techniques in MRI studies are discussed. Examples of contrast-enhanced imaging using advanced pulse sequences are discussed with the main focus on important studies in the field of neurological diseases. In addition, T1 contrast agents such as gadolinium chelates are compared with the T2 contrast agents mainly made of superparamagnetic inorganic metal nanoparticles.

scholarly journals Functional Foods: An Approach to Modulate Molecular Mechanisms of Alzheimer’s Disease

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2347
Author(s):  
Anna Atlante ◽  
Giuseppina Amadoro ◽  
Antonella Bobba ◽  
Valentina Latina
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Food Product ◽  
Neuroprotective Effects ◽  
The Road ◽  
Beneficial Effects ◽  
Β Amyloid ◽  
The Brain

A new epoch is emerging with intense research on nutraceuticals, i.e., “food or food product that provides medical or health benefits including the prevention and treatment of diseases”, such as Alzheimer’s disease. Nutraceuticals act at different biochemical and metabolic levels and much evidence shows their neuroprotective effects; in particular, they are able to provide protection against mitochondrial damage, oxidative stress, toxicity of β-amyloid and Tau and cell death. They have been shown to influence the composition of the intestinal microbiota significantly contributing to the discovery that differential microorganisms composition is associated with the formation and aggregation of cerebral toxic proteins. Further, the routes of interaction between epigenetic mechanisms and the microbiota–gut–brain axis have been elucidated, thus establishing a modulatory role of diet-induced epigenetic changes of gut microbiota in shaping the brain. This review examines recent scientific literature addressing the beneficial effects of some natural products for which mechanistic evidence to prevent or slowdown AD are available. Even if the road is still long, the results are already exceptional.

Gut Microbiota and Alzheimer’s Disease: Experimental Evidence and Clinical Reality

2021 ◽  
Vol 18 ◽  
Author(s):  
Sarama Saha ◽  
Sukhpal Singh ◽  
Suvarna Prasad ◽  
Amit Mittal ◽  
Anil Kumar Sharma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Experimental Evidence ◽  
Molecular Mechanisms ◽  
Bacterial Flora ◽  
Experimental Studies ◽  
The Elderly ◽  
The Impact ◽  
The Brain

: Alzheimer’s disease (AD) is characterized by progressive death of neuronal cells in the regions of the brain concerned with memory and cognition, and is the major cause of dementia in the elderly population. Various molecular mechanisms, metabolic risk factors and environmental triggers contributing to the genesis and progression of AD are under intense investigations. The present review has dealt with the impact of a highly discussed topic of gut microbiota affecting the neurodegeneration in the AD brain. A detailed description of the composition of gut bacterial flora and its interaction with the host has been presented, followed by an analysis of key concepts of bi- directional communication between gut microbiota and the brain. The substantial experimental evidence of gut microbiota affecting the neurodegenerative process in experimental AD models has been described next in this review, and finally, the limitations of such experimental studies vis-a- vis the actual disease and the paucity of clinical data on this topic have also been mentioned.

Expression of CD40 in the brain of Alzheimer’s disease and other neurological diseases

2000 ◽  
Vol 885 (1) ◽  
pp. 117-121 ◽  
Author(s):  
Takashi Togo ◽  
Haruhiko Akiyama ◽  
Hiromi Kondo ◽  
Kenji Ikeda ◽  
Masanori Kato ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurological Diseases ◽  
The Brain

scholarly journals Diabetes and Alzheimer’s Disease: Might Mitochondrial Dysfunction Help Deciphering the Common Path?

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1257
Author(s):  
Maria Assunta Potenza ◽  
Luca Sgarra ◽  
Vanessa Desantis ◽  
Carmela Nacci ◽  
Monica Montagnani
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Senile Plaques ◽  
Mitochondrial Activity ◽  
Enhanced Production ◽  
The Common ◽  
The Brain

A growing number of clinical and epidemiological studies support the hypothesis of a tight correlation between type 2 diabetes mellitus (T2DM) and the development risk of Alzheimer’s disease (AD). Indeed, the proposed definition of Alzheimer’s disease as type 3 diabetes (T3D) underlines the key role played by deranged insulin signaling to accumulation of aggregated amyloid beta (Aβ) peptides in the senile plaques of the brain. Metabolic disturbances such as hyperglycemia, peripheral hyperinsulinemia, dysregulated lipid metabolism, and chronic inflammation associated with T2DM are responsible for an inefficient transport of insulin to the brain, producing a neuronal insulin resistance that triggers an enhanced production and deposition of Aβ and concomitantly contributes to impairment in the micro-tubule-associated protein Tau, leading to neural degeneration and cognitive decline. Furthermore, the reduced antioxidant capacity observed in T2DM patients, together with the impairment of cerebral glucose metabolism and the decreased performance of mitochondrial activity, suggests the existence of a relationship between oxidative damage, mitochondrial impairment, and cognitive dysfunction that could further reinforce the common pathophysiology of T2DM and AD. In this review, we discuss the molecular mechanisms by which insulin-signaling dysregulation in T2DM can contribute to the pathogenesis and progression of AD, deepening the analysis of complex mechanisms involved in reactive oxygen species (ROS) production under oxidative stress and their possible influence in AD and T2DM. In addition, the role of current therapies as tools for prevention or treatment of damage induced by oxidative stress in T2DM and AD will be debated.

Diversity and Regulation of Astrocyte Neurotoxicity in Alzheimer's Disease

2021 ◽  
Vol 18 ◽  
Author(s):  
Sadayuki Hashioka ◽  
James G. McLarnon ◽  
Andis Klegeris
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Nuclear Imaging ◽  
Resonance Spectroscopy ◽  
Tnf Α ◽  
Factor Α ◽  
The Brain ◽  
Harmful Effects ◽  
Necrosis Factor

: Astrocytes contribute to brain development and homeostasis and support diverse functions of neurons. These cells also respond to the pathological processes in Alzheimer’s disease (AD). There is still considerable debate concerning the overall contribution of astrocytes to AD pathogenesis since both the protective and harmful effects of these cells on neuronal survival have been documented. This review focuses exclusively on the neurotoxic potential of astrocytes while acknowledging that these cells can contribute to neurodegeneration through other mechanisms, for example, by lowered neurotrophic support. We identify reactive oxygen and nitrogen species, tumor necrosis factor α (TNF-α), glutamate, and matrix metalloproteinase (MMP)-9 as molecules that can be directly toxic to neurons and are released by reactive astrocytes. There is also considerable evidence suggesting their involvement in AD pathogenesis. We further discuss the signaling molecules that trigger the neurotoxic response of astrocytes with a focus on human cells. We also highlight microglia, the immune cells of the brain, as critical regulators of astrocyte neurotoxicity. Nuclear imaging and magnetic resonance spectroscopy (MRS) could be used to confirm the contribution of astrocyte neurotoxicity to AD progression. The molecular mechanisms discussed in this review could be targeted in the development of novel therapies for AD.

scholarly journals Downregulation of TREM2 Expression Exacerbates Neuroinflammatory Responses Through TLR4-Mediated MAPK Signaling Pathway in a Transgenic Mouse Model of Alzheimer’s Disease

2021 ◽  
Author(s):  
John Bosco Ruganzu ◽  
Xiaoqian Peng ◽  
Yingying He ◽  
Xiangyuan Wu ◽  
Quzhao Zheng ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mechanistic Study ◽  
Model Of Alzheimer’S Disease ◽  
Bv2 Cells ◽  
The Brain

Abstract Activation of glial cells and neuroinflammation play an important role in the onset and development of Alzheimer’s disease (AD). Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglia-specific receptor in the brain that is involved in regulating neuroinflammation. However, the precise effects of TREM2 on neuroinflammatory responses and its underlying molecular mechanisms in AD have not been studied in detail. Here, we employed a lentiviral-mediated strategy to downregulation of TREM2 expression on microglia in the brain of APPswe/PS1dE9 (APP/PS1) transgenic mice and BV2 cells. Our results showed that TREM2 downregulation significantly aggravated AD-related neuropathology including Aβ accumulation, peri-plaque microgliosis and astrocytosis, as well as neuronal and synapse-associated proteins loss, which was accompanied by a decline in cognitive ability. The further mechanistic study revealed that downregulation of TREM2 expression initiated neuroinflammatory responses through toll-like receptor 4 (TLR4)-mediated mitogen-activated protein kinase (MAPK) signaling pathway and subsequent stimulating the production of pro-inflammatory cytokines in vivo and in vitro. Moreover, blockade of p38, JNK, and ERK1/2 inhibited the release of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) induced by Aβ1−42 in TREM2-knocked down BV2 cells. Taken together, these findings indicated that TREM2 might be a potential therapeutic target for AD and other neuroinflammation related diseases.

scholarly journals The Anti-Amyloidogenic Action of Doxycycline: A Molecular Dynamics Study on the Interaction with Aβ42

2019 ◽  
Vol 20 (18) ◽  
pp. 4641 ◽  
Author(s):  
Alfonso Gautieri ◽  
Marten Beeg ◽  
Marco Gobbi ◽  
Federica Rigoldi ◽  
Laura Colombo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Dynamics ◽  
Molecular Mechanisms ◽  
Amyloid Fibrils ◽  
Neurological Diseases ◽  
Fibrillar Structure ◽  
Structure Based Drug Design

The pathological aggregation of amyloidogenic proteins is a hallmark of many neurological diseases, including Alzheimer’s disease and prion diseases. We have shown both in vitro and in vivo that doxycycline can inhibit the aggregation of Aβ42 amyloid fibrils and disassemble mature amyloid fibrils. However, the molecular mechanisms of the drug’s anti-amyloidogenic property are not understood. In this study, a series of molecular dynamics simulations were performed to explain the molecular mechanism of the destabilization of Aβ42 fibrils by doxycycline and to compare the action of doxycycline with those of iododoxorubicin (a toxic structural homolog of tetracyclines), curcumin (known to have anti-amyloidogenic activity) and gentamicin (an antibiotic with no experimental evidence of anti-amyloidogenic properties). We found that doxycycline tightly binds the exposed hydrophobic amino acids of the Aβ42 amyloid fibrils, partly leading to destabilization of the fibrillar structure. Clarifying the molecular determinants of doxycycline binding to Aβ42 may help devise further strategies for structure-based drug design for Alzheimer’s disease.

scholarly journals A New Perspective on the Treatment of Alzheimer’s Disease and Sleep Deprivation-Related Consequences: Can Curcumin Help?

2022 ◽  
Vol 2022 ◽  
pp. 1-23
Author(s):  
Esra Küpeli Akkol ◽  
Hilal Bardakcı ◽  
Çiğdem Yücel ◽  
Gökçe Şeker Karatoprak ◽  
Büşra Karpuz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sleep Deprivation ◽  
Sleep Disturbances ◽  
Neurological Diseases ◽  
Clinical Signs ◽  
Scientific Data ◽  
Age Related ◽  
Different Types ◽  
The Brain

Sleep disturbances, as well as sleep-wake rhythm disorders, are characteristic symptoms of Alzheimer’s disease (AD) that may head the other clinical signs of this neurodegenerative disease. Age-related structural and physiological changes in the brain lead to changes in sleep patterns. Conditions such as AD affect the cerebral cortex, basal forebrain, locus coeruleus, and the hypothalamus, thus changing the sleep-wake cycle. Sleep disorders likewise adversely affect the course of the disease. Since the sleep quality is important for the proper functioning of the memory, impaired sleep is associated with problems in the related areas of the brain that play a key role in learning and memory functions. In addition to synthetic drugs, utilization of medicinal plants has become popular in the treatment of neurological diseases. Curcuminoids, which are in a diarylheptanoid structure, are the main components of turmeric. Amongst them, curcumin has multiple applications in treatment regimens of various diseases such as cardiovascular diseases, obesity, cancer, inflammatory diseases, and aging. Besides, curcumin has been reported to be effective in different types of neurodegenerative diseases. Scientific studies exclusively showed that curcumin leads significant improvements in the pathological process of AD. Yet, its low solubility hence low bioavailability is the main therapeutic limitation of curcumin. Although previous studies have focused different types of advanced nanoformulations of curcumin, new approaches are needed to solve the solubility problem. This review summarizes the available scientific data, as reported by the most recent studies describing the utilization of curcumin in the treatment of AD and sleep deprivation-related consequences.

scholarly journals AβInternalization by Neurons and Glia

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Amany Mohamed ◽  
Elena Posse de Chaves
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Strong Evidence ◽  
Molecular Mechanisms ◽  
Neuronal Dysfunction ◽  
Intracellular Accumulation ◽  
Extracellular Milieu ◽  
Long Time ◽  
The Brain

In the brain, the amyloidβpeptide (Aβ) exists extracellularly and inside neurons. The intracellular accumulation of Aβin Alzheimer's disease brain has been questioned for a long time. However, there is now sufficient strong evidence indicating that accumulation of Aβinside neurons plays an important role in the pathogenesis of Alzheimer's disease. Intraneuronal Aβoriginates from intracellular cleavage of APP and from Aβinternalization from the extracellular milieu. We discuss here the different molecular mechanisms that are responsible for Aβinternalization in neurons and the links between Aβinternalization and neuronal dysfunction and death. A brief description of Aβuptake by glia is also presented.

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