scholarly journals The Critical Role of Nurr1 as a Mediator and Therapeutic Target in Alzheimer’s Disease-related Pathogenesis

2020 ◽  
Vol 11 (3) ◽  
pp. 705 ◽  
Author(s):  
Seong Gak Jeon ◽  
Anji Yoo ◽  
Dong Wook Chun ◽  
Sang Bum Hong ◽  
Hyunju Chung ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Target ◽  
Critical Role

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.

scholarly journals Corticotropin releasing factor-binding protein (CRF-BP) as a potential new therapeutic target in Alzheimer’s disease and stress disorders

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Dorien Vandael ◽  
Natalia V. Gounko
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Therapeutic Target ◽  
Life Stress ◽  
Binding Protein ◽  
Critical Role ◽  
Treatment Strategies ◽  
Corticotropin Releasing Factor ◽  
Stress Disorders

Abstract Alzheimer’s disease is the most common cause of dementia and one of the most complex human neurodegenerative diseases. Numerous studies have demonstrated a critical role of the environment in the pathogenesis and pathophysiology of the disease, where daily life stress plays an important role. A lot of epigenetic studies have led to the conclusion that chronic stress and stress-related disorders play an important part in the onset of neurodegenerative disorders, and an enormous amount of research yielded valuable discoveries but has so far not led to the development of effective treatment strategies for Alzheimer’s disease. Corticotropin-releasing factor (CRF) is one of the major hormones and at the same time a neuropeptide acting in stress response. Deregulation of protein levels of CRF is involved in the pathogenesis of Alzheimer’s disease, but little is known about the precise roles of CRF and its binding protein, CRF-BP, in neurodegenerative diseases. In this review, we summarize the key evidence for and against the involvement of stress-associated modulation of the CRF system in the pathogenesis of Alzheimer’s disease and discuss how recent findings could lead to new potential treatment possibilities in Alzheimer’s disease by using CRF-BP as a therapeutic target.

scholarly journals Alzheimer's disease and periodontitis - an elusive link

2014 ◽  
Vol 60 (2) ◽  
pp. 173-180 ◽  
Author(s):  
Abhijit N. Gurav
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Cytokines ◽  
Critical Role ◽  
Anaerobic Bacteria ◽  
Systemic Infection ◽  
Low Grade ◽  
Inflammatory Status ◽  
Pro Inflammatory Cytokines

Alzheimer's disease is the preeminent cause and commonest form of dementia. It is clinically characterized by a progressive descent in the cognitive function, which commences with deterioration in memory. The exact etiology and pathophysiologic mechanism of Alzheimer's disease is still not fully understood. However it is hypothesized that, neuroinflammation plays a critical role in the pathogenesis of Alzheimer's disease. Alzheimer's disease is marked by salient inflammatory features, characterized by microglial activation and escalation in the levels of pro-inflammatory cytokines in the affected regions. Studies have suggested a probable role of systemic infection conducing to inflammatory status of the central nervous system. Periodontitis is common oral infection affiliated with gram negative, anaerobic bacteria, capable of orchestrating localized and systemic infections in the subject. Periodontitis is known to elicit a "low grade systemic inflammation" by release of pro-inflammatory cytokines into systemic circulation. This review elucidates the possible role of periodontitis in exacerbating Alzheimer's disease. Periodontitis may bear the potential to affect the onset and progression of Alzheimer's disease. Periodontitis shares the two important features of Alzheimer's disease namely oxidative damage and inflammation, which are exhibited in the brain pathology of Alzheimer's disease. Periodontitis can be treated and hence it is a modifiable risk factor for Alzheimer's disease.

scholarly journals Microglial ApoD Induced NLRC4 Inflammasome Activation Promotes Alzheimer’s Disease Progression

2021 ◽  
Author(s):  
Yaliang Yu ◽  
Jianzhou Lv ◽  
Dan Ma ◽  
Ya Han ◽  
Yaheng Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Critical Role ◽  
Microglia Activation ◽  
Inflammatory Factors ◽  
Inflammasome Activation ◽  
Cellular Interactions ◽  
Brain Functions ◽  
Chronic Neuroinflammation

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disease with no effective therapies. It’s well-known that chronic neuroinflammation plays a critical role in the onset and progression of AD. Proper neuronal-microglial interactions are essential for brain functions. However, as the main existence of immune cells, determining the role of microglia in Alzheimer’s neuroinflammation and the associated molecular basis has been challenging. Herein, the inflammatory factors in the sera of AD patients were detected and the association with microglia activation was analyzed. The mechanism regarding the microglial inflammation was investigated. The IL6 and TNF-α were found to be significantly increased in the AD stage. Further analysis revealed microglia were extensively activated in AD cerebra releasing mounts of cytokines to impair the neural stem cells (NSCs) function. Moreover, ApoD induced NLRC4 inflammasome was activated in microglia, which gave rise to the proinflammatory phenotype. Targeting the microglial ApoD promoted NSCs self-renewal and inhibited neuron apoptosis. These findings demonstrate the critical role of ApoD in microglial inflammasome activation, and for the first time reveal that microglia-induced inflammation suppresses neuronal proliferation. Our studies establish the cellular basis for microglia activation in AD progression, and shed lights on cellular interactions important for AD treatment.

scholarly journals New Insights on the Role of Manganese in Alzheimer’s Disease and Parkinson’s Disease

2019 ◽  
Vol 16 (19) ◽  
pp. 3546 ◽  
Author(s):  
Airton Cunha Martins ◽  
Patricia Morcillo ◽  
Omamuyovwi Meashack Ijomone ◽  
Vivek Venkataramani ◽  
Fiona Edith Harrison ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Critical Role ◽  
Essential Trace Element ◽  
Neuronal Function ◽  
Therapy Options ◽  
Physiological Processes

Manganese (Mn) is an essential trace element that is naturally found in the environment and is necessary as a cofactor for many enzymes and is important in several physiological processes that support development, growth, and neuronal function. However, overexposure to Mn may induce neurotoxicity and may contribute to the development of Alzheimer’s disease (AD) and Parkinson’s disease (PD). The present review aims to provide new insights into the involvement of Mn in the etiology of AD and PD. Here, we discuss the critical role of Mn in the etiology of these disorders and provide a summary of the proposed mechanisms underlying Mn-induced neurodegeneration. In addition, we review some new therapy options for AD and PD related to Mn overload.

scholarly journals May “Mitochondrial Eve” and Mitochondrial Haplogroups Play a Role in Neurodegeneration and Alzheimer's Disease?

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Elena Caldarazzo Ienco ◽  
Costanza Simoncini ◽  
Daniele Orsucci ◽  
Loredana Petrucci ◽  
Massimiliano Filosto ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Critical Role ◽  
Protective Role ◽  
Oxygen Species ◽  
Mitochondrial Haplogroups ◽  
Normal Ageing ◽  
Apoptotic Pathways ◽  
Mitochondrial Eve

Mitochondria, the powerhouse of the cell, play a critical role in several metabolic processes and apoptotic pathways. Multiple evidences suggest that mitochondria may be crucial in ageing-related neurodegenerative diseases. Moreover, mitochondrial haplogroups have been linked to multiple area of medicine, from normal ageing to diseases, including neurodegeneration. Polymorphisms within the mitochondrial genome might lead to impaired energy generation and to increased amount of reactive oxygen species, having either susceptibility or protective role in several diseases. Here, we highlight the role of the mitochondrial haplogroups in the pathogenetic cascade leading to diseases, with special attention to Alzheimer's disease.

The potential role of microRNA-146 in Alzheimer’s disease: Biomarker or therapeutic target?

2012 ◽  
Vol 78 (3) ◽  
pp. 398-401 ◽  
Author(s):  
Li-Ling Wang ◽  
Yue Huang ◽  
Gang Wang ◽  
Sheng-Di Chen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Target ◽  
Potential Role ◽  
Disease Biomarker

Inhibition of microRNA-155 Alleviates Cognitive Impairment in Alzheimer’s Disease and Involvement of Neuroinflammation

2019 ◽  
Vol 16 (6) ◽  
pp. 473-482 ◽  
Author(s):  
Dandan Liu ◽  
Dandan Zhao ◽  
Yingkai Zhao ◽  
Yan Wang ◽  
Yong Zhao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Functions ◽  
Spatial Working Memory ◽  
Critical Role ◽  
Learning Performance ◽  
Intracerebroventricular Infusion ◽  
Tnf Α ◽  
Current Report

Background: Neuroinflammation has important effects on cognitive functions in the pathophysiological process of Alzheimer’s Disease (AD). In the current report, we determined the effects of microRNA-155 (miR-155) on the levels of IL-1β, IL-6 and TNF-α, and their respective receptors in the hippocampus using a rat model of AD. Methods: Real-time RT-PCR, ELISA and western blot analysis were used to examine the miR-155, PICs and PIC receptors. The Morris water maze and spatial working memory tests were used to assess cognitive functions. Results: miR-155 was increased in the hippocampus of AD rats, accompanied by amplification of IL-1β, IL-6 and TNF-α. Intracerebroventricular infusion of miR-155 inhibitor, but not its scramble attenuated the increases of IL-1β, IL-6 and TNF-α and upregulation of their receptors. MiR-155 inhibitor also attenuated upregulation of apoptotic Caspase-3 in the hippocampus of AD rats. Notably, inhibition of miR- 155 or PIC receptors largely recovered the impaired learning performance in AD rat. Conclusion: We showed the critical role of miR-155 in regulating the memory impairment in AD rats likely via engagement of neuroinflammatory mechanisms, suggesting that miR-155 and its signaling molecules may present prospects in preventing and/or improving the development of the impaired cognitive functions in AD.

Sign in / Sign up

Export Citation Format

Share Document