scholarly journals The potential role for sphingolipids in neuropathogenesis of Alzheimer’s disease

2013 ◽  
Vol 59 (1) ◽  
pp. 25-50 ◽  
Author(s):  
A.V. Alessenko
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Role ◽  
Potential Role ◽  
Early Stage ◽  
New Drugs ◽  
Neuronal Function ◽  
Sphingosine 1 Phosphate ◽  
The Brain

The review discusses the functional role of sphingolipids in the pathogenesis of Alzheimer's disease. Certain evidence exist that the imbalance of sphingolipids such as sphingomyelin, ceramide, sphingosine, sphingosine-1-phosphate and galactosylceramide in the brain of animals and humans, in the cerebrospinal fluid and blood plasma of patients with Alzheimer's disease play a crucial role in neuronal function by regulating growth, differentiation and cell death in CNS. Activation of sphingomyelinase, which leads to the accumulation of the proapoptotic agent, ceramide, can be considered as a new mechanism for AD and may be a prerequisite for the treatment of this disease by using drugs that inhibit sphingomyelinase activity. The role of sphingolipids as biomarkers for the diagnosis of the early stage of Alzheimer's disease and monitoring the effectiveness of treatment with new drugs is discussed.

scholarly journals Role of Body-Fluid Biomarkers in Alzheimer’s Disease Diagnosis

Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 326 ◽  
Author(s):  
Thuy Trang Nguyen ◽  
Qui Thanh Hoai Ta ◽  
Thi Kim Oanh Nguyen ◽  
Thi Thuy Dung Nguyen ◽  
Van Giau Vo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Body Fluid ◽  
Early Stage ◽  
Disease Diagnosis ◽  
Clinical Diagnostics ◽  
Research Priority ◽  
Development And Validation ◽  
The Brain

Alzheimer’s disease (AD) is a complex neurodegenerative disease that requires extremely specific biomarkers for its diagnosis. For current diagnostics capable of identifying AD, the development and validation of early stage biomarkers is a top research priority. Body-fluid biomarkers might closely reflect synaptic dysfunction in the brain and, thereby, could contribute to improving diagnostic accuracy and monitoring disease progression, and serve as markers for assessing the response to disease-modifying therapies at early onset. Here, we highlight current advances in the research on the capabilities of body-fluid biomarkers and their role in AD pathology. Then, we describe and discuss current applications of the potential biomarkers in clinical diagnostics in AD.

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.

scholarly journals Using Drosophila Models of Amyloid Toxicity to Study Autophagy in the Pathogenesis of Alzheimer’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Louise O’Keefe ◽  
Donna Denton
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Function ◽  
Amyloid Toxicity ◽  
Cellular Pathways ◽  
Toxic Peptides ◽  
The Brain ◽  
Prevalent Form ◽  
Drosophila Models

Autophagy is a conserved catabolic pathway that involves the engulfment of cytoplasmic components such as large protein aggregates and organelles that are delivered to the lysosome for degradation. This process is important in maintaining neuronal function and raises the possibility of a role for autophagy in neurodegenerative diseases. Alzheimer’s disease (AD) is the most prevalent form of these diseases and is characterized by the accumulation of amyloid plaques in the brain which arise due to the misfolding and aggregation of toxic peptides, including amyloid beta (Aβ). There is substantial evidence from both AD patients and animal models that autophagy is dysregulated in this disease. However, it remains to be determined whether this is protective or pathogenic as there is evidence that autophagy can act to promote the degradation as well as function in the generation of toxic Aβ peptides. Understanding the molecular details of the extensive crosstalk that occurs between the autophagic and endolysosomal cellular pathways is essential for identifying the molecular details of amyloid toxicity. Drosophila models that express the toxic proteins that aggregate in AD have been generated and have been shown to recapitulate hallmarks of the disease. Here we focus on what is known about the role of autophagy in amyloid toxicity in AD from mammalian models and how Drosophila models can be used to further investigate AD pathogenesis.

A Review of the Brain-Gut-Microbiome Axis and the Potential Role of Microbiota in Alzheimer’s Disease

2020 ◽  
Vol 73 (3) ◽  
pp. 849-865 ◽  
Author(s):  
Miao Sun ◽  
Kai Ma ◽  
Jie Wen ◽  
Guangxian Wang ◽  
Changliang Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiome ◽  
Potential Role ◽  
The Brain

scholarly journals CSF total tau, plasma and CSF p tau 181 associated with structural changes in the early stage of Alzheimer's disease

2020 ◽  
Author(s):  
Fardin Nabizadeh ◽  
Mohammad Reza Rostami ◽  
mohammad Balabandian ◽  
Niloufar Ahmadi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Structural Changes ◽  
Clinical Symptoms ◽  
Early Stage ◽  
Cross Sectional ◽  
Total Tau ◽  
Preclinical Ad ◽  
The Brain

Abstract Alzheimer's disease (AD) is the most important cause of dementia and is a serious concern for individuals and governments worldwide. Changes in the brain appear about 15 years before the first clinical symptoms; with this in mind, it can clear the role of biomarkers in monitoring Alzheimer's development. P tau 181 level in plasma recently emerged as a new biomarker and rises obviously in AD patients, preclinical AD, and MCI patients. The role of gray matter atrophy and white matter damages in cognitive decline is well established, which is detectable by magnetic resonance imaging (MRI). In this investigation, we measured the association between CSF (total tau, and p tau 181) and plasma p tau 181 with structural changes (cortical thickness, cortical volume, surface area, and subcortical volume) in MCI patients. We performed a cross-sectional study on the ADNI cohort between 461 MCI patients. Results of voxel-wise partial correlation analysis in our participants showed a significant correlation between plasma p tau 181, CSF total tau and p tau 181 with changes in structural values in different regions. Our study revealed a significant correlation between plasma p tau and structural changes in the brain regions associated with Alzheimer's disease physiopathology. These results provide evidence for using plasma p tau 181 as a diagnostic factor in the early onset of AD patients and neurodegeneration.

Role of Nanomedicines in Delivery of Anti-Acetylcholinesterase Compounds to the Brain in Alzheimer’s Disease

2014 ◽  
Vol 13 (8) ◽  
pp. 1315-1324 ◽  
Author(s):  
Mohammad Ahmad ◽  
Javed Ahmad ◽  
Saima Amin ◽  
Mahfoozur Rahman ◽  
Mohammad Anwar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
The Brain

scholarly journals Peptides Derived from Growth Factors to Treat Alzheimer’s Disease

2021 ◽  
Vol 22 (11) ◽  
pp. 6071
Author(s):  
Suzanne Gascon ◽  
Jessica Jann ◽  
Chloé Langlois-Blais ◽  
Mélanie Plourde ◽  
Christine Lavoie ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Growth Factors ◽  
Signaling Pathways ◽  
Brain Structures ◽  
Therapeutic Strategies ◽  
Native Proteins ◽  
Receptor Sites ◽  
The Brain

Alzheimer’s disease (AD) is a devastating neurodegenerative disease characterized by progressive neuron losses in memory-related brain structures. The classical features of AD are a dysregulation of the cholinergic system, the accumulation of amyloid plaques, and neurofibrillary tangles. Unfortunately, current treatments are unable to cure or even delay the progression of the disease. Therefore, new therapeutic strategies have emerged, such as the exogenous administration of neurotrophic factors (e.g., NGF and BDNF) that are deficient or dysregulated in AD. However, their low capacity to cross the blood–brain barrier and their exorbitant cost currently limit their use. To overcome these limitations, short peptides mimicking the binding receptor sites of these growth factors have been developed. Such peptides can target selective signaling pathways involved in neuron survival, differentiation, and/or maintenance. This review focuses on growth factors and their derived peptides as potential treatment for AD. It describes (1) the physiological functions of growth factors in the brain, their neuronal signaling pathways, and alteration in AD; (2) the strategies to develop peptides derived from growth factor and their capacity to mimic the role of native proteins; and (3) new advancements and potential in using these molecules as therapeutic treatments for AD, as well as their limitations.

scholarly journals Alzheimer’s Disease Pathogenesis: Role of Autophagy and Mitophagy Focusing in Microglia

2021 ◽  
Vol 22 (7) ◽  
pp. 3330
Author(s):  
Mehdi Eshraghi ◽  
Aida Adlimoghaddam ◽  
Amir Mahmoodzadeh ◽  
Farzaneh Sharifzad ◽  
Hamed Yasavoli-Sharahi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Target ◽  
Neurological Disorder ◽  
Inflammatory Cells ◽  
Disease Pathogenesis ◽  
Current Review ◽  
The Brain ◽  
Comprehensive Discussion

Alzheimer’s disease (AD) is a debilitating neurological disorder, and currently, there is no cure for it. Several pathologic alterations have been described in the brain of AD patients, but the ultimate causative mechanisms of AD are still elusive. The classic hallmarks of AD, including am-yloid plaques (Aβ) and tau tangles (tau), are the most studied features of AD. Unfortunately, all the efforts targeting these pathologies have failed to show the desired efficacy in AD patients so far. Neuroinflammation and impaired autophagy are two other main known pathologies in AD. It has been reported that these pathologies exist in AD brain long before the emergence of any clinical manifestation of AD. Microglia are the main inflammatory cells in the brain and are considered by many researchers as the next hope for finding a viable therapeutic target in AD. Interestingly, it appears that the autophagy and mitophagy are also changed in these cells in AD. Inside the cells, autophagy and inflammation interact in a bidirectional manner. In the current review, we briefly discussed an overview on autophagy and mitophagy in AD and then provided a comprehensive discussion on the role of these pathways in microglia and their involvement in AD pathogenesis.

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