scholarly journals The central role of T-cell memory in Alzheimer’s disease vaccination

2010 ◽  
Vol 1 (1) ◽  
pp. 5
Author(s):  
Brian Giunta ◽  
Amanda Ruscin ◽  
Jon Salemi ◽  
Alan Wolfson ◽  
Francisco Fernandez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
T Cell ◽  
Animal Models ◽  
The Elderly ◽  
Active Immunization ◽  
T Cell Subsets ◽  
Neurocognitive Deficits ◽  
Cell Reactivity

Alzheimer's disease (AD) is the most common progressive neurodegenerative brain disease as well as the most common dementia among the elderly. In the future as the average lifespan continues to extend, the number of AD patients will continue to grow. Amyloid-beta (Aβ) peptides, in both soluble oligomeric, and insoluble forms, are key in the neuropathogenesis of AD and have thus been a therapeutic target for vaccines. Multiple Aβ vaccination strategies in animal models of AD have demonstrated a marked reduction in both amyloid burden and neurocognitive deficits. Due to the success of these studies, initial human clinical trials of an active Aβ vaccine were conducted. These were discontinued due to the development of meningoencephalitis in approximately 6% of the vaccinated AD patients. Studies examining the brains of Aβ-vaccinated patients developing meningoencephalitis implicate Aβ-reactive T-cell subsets as major components of this deleterious response to active Aβ vaccination. To subvert possible meningoencephalitis resulting from Aβ vaccination second generation of vaccines has been more recently developed. These however have met with little success in humans. To build on these findings, an understanding of the role of T-cells in vaccination against Aβ is presented in this review. Various methods of Aβ immunotherapy are reviewed including studies in both animal models and humans. Recent works suggest that Aβ-derived peptides delivered intranasally or transcutaneously results in effective clearance of Aβ plaques and improvement of cognitive function in animal models of AD. Moreover, undesired T-cell reactivity appeared to be considerably reduced compared with other active immunization strategies. In spite of the past clinical studies, these findings imply that Aβ vaccination may be both efficacious and safe depending route of delivery, adjuvant choice, and Aβ epitope administered.

The role of T cell reactivity to A-beta amyloid peptide in the pathogenic processes associated with Alzheimer's disease

2000 ◽  
Vol 21 ◽  
pp. 23 ◽  
Author(s):  
Alon Monsonego ◽  
Ruth Maron ◽  
Amit Bar-Or ◽  
Jeff I. Krieger ◽  
Dennis Selkoe ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
T Cell ◽  
Beta Amyloid ◽  
Amyloid Peptide ◽  
Cell Reactivity ◽  
Beta Amyloid Peptide ◽  
T Cell Reactivity

scholarly journals Isovitexin modulates autophagy in Alzheimer’s disease via miR-107 signalling

2020 ◽  
Vol 11 (1) ◽  
pp. 391-401
Author(s):  
Jiang Cheng ◽  
Guowei Wang ◽  
Na Zhang ◽  
Fang Li ◽  
Lina Shi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Loss ◽  
The Elderly ◽  
Tnf Α ◽  
Autophagic Process ◽  
Molecular Signals ◽  
Ad Mouse Model ◽  
Mtor Signalling

AbstractBackground:Alzheimer’s disease (AD) is an ultimately fatal, degenerative brain disease in the elderly people. In the current work, we assessed the defensive capability of isovitexin (IVX) through an intracerebroventricular injection of streptozotocin (STZ)-induced AD mouse model.Methods:Mice were separated into four cohorts: sham-operated control mice; STZ-intoxicated Alzheimer’s mice; IVX cohort, IVX + STZ; and Ant-107 cohort, antagomiR-107 + IVX/STZ as in the IVX cohort.Results:The outcomes indicated that IVX administration ameliorated spatial memory loss and blunted a cascade of neuro-noxious episodes – including increased amyloid-beta (Aβ) and degraded myelin basic protein burden, neuroinflammation (represented by elevated caspase-1, TNF-α and IL-6 levels) and autophagic dysfunction (represented by altered LC3-II, Atg7 and beclin-1 expressions) – via the inhibition of PI3K/Akt/mTOR signalling axis. We considered the question of whether the epigenetic role of microRNA-107 (miR-107) has any impact on these events, by using antagomiR-107.Conclusion:This probing underscored that miR-107 could be a pivotal regulatory button in the activation of molecular signals linked with the beneficial autophagic process and anti-inflammatory activities in relation to IVX treatment. Hence, this report exemplifies that IVX could guard against Aβ toxicity and serve as an effectual treatment for patients afflicted with AD.

P2-004: The role of CD8 T cell and its receptor change in Alzheimer's disease

2012 ◽  
Vol 8 (4S_Part_7) ◽  
pp. P265-P265
Author(s):  
Chuanhai Cao ◽  
Xiaoyang Lin ◽  
Wenshi Wang ◽  
Yaqiong Li ◽  
Jianfeng Cai ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
T Cell ◽  
Cd8 T Cell

scholarly journals Astrocytes and Adenosine A2A Receptors: Active Players in Alzheimer’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Cátia R. Lopes ◽  
Rodrigo A. Cunha ◽  
Paula Agostinho
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
The Elderly ◽  
Synaptic Function ◽  
Morphological Alterations ◽  
Functional Changes ◽  
A2a Receptors ◽  
Novel Therapeutic Strategies

Astrocytes, through their numerous processes, establish a bidirectional communication with neurons that is crucial to regulate synaptic plasticity, the purported neurophysiological basis of memory. This evidence contributed to change the classic “neurocentric” view of Alzheimer’s disease (AD), being astrocytes increasingly considered a key player in this neurodegenerative disease. AD, the most common form of dementia in the elderly, is characterized by a deterioration of memory and of other cognitive functions. Although, early cognitive deficits have been associated with synaptic loss and dysfunction caused by amyloid-β peptides (Aβ), accumulating evidences support a role of astrocytes in AD. Astrocyte atrophy and reactivity occurring at early and later stages of AD, respectively, involve morphological alterations that translate into functional changes. However, the main signals responsible for astrocytic alterations in AD and their impact on synaptic function remain to be defined. One possible candidate is adenosine, which can be formed upon extracellular catabolism of ATP released by astrocytes. Adenosine can act as a homeostatic modulator and also as a neuromodulator at the synaptic level, through the activation of adenosine receptors, mainly of A1R and A2AR subtypes. These receptors are also present in astrocytes, being particularly relevant in pathological conditions, to control the morphofunctional responses of astrocytes. Here, we will focus on the role of A2AR, since they are particularly associated with neurodegeneration and also with memory processes. Furthermore, A2AR levels are increased in the AD brain, namely in astrocytes where they can control key astrocytic functions. Thus, unveiling the role of A2AR in astrocytes function might shed light on novel therapeutic strategies for AD.

scholarly journals Overview of Alzheimer’s Disease and Some Therapeutic Approaches Targeting Aβby Using Several Synthetic and Herbal Compounds

2016 ◽  
Vol 2016 ◽  
pp. 1-22 ◽  
Author(s):  
Sandeep Kumar Singh ◽  
Saurabh Srivastav ◽  
Amarish Kumar Yadav ◽  
Saripella Srikrishna ◽  
George Perry
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Neurodegenerative Disease ◽  
Therapeutic Approaches ◽  
Age Related

Alzheimer’s disease (AD) is a complex age-related neurodegenerative disease. In this review, we carefully detail amyloid-βmetabolism and its role in AD. We also consider the various genetic animal models used to evaluate therapeutics. Finally, we consider the role of synthetic and plant-based compounds in therapeutics.

scholarly journals Potential Role of Phenolic Extracts of Mentha in Managing Oxidative Stress and Alzheimer’s Disease

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 631
Author(s):  
Doaa M. Hanafy ◽  
Geoffrey E. Burrows ◽  
Paul D. Prenzler ◽  
Rodney A. Hill
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Potential Role ◽  
The Elderly ◽  
Future Research ◽  
Phenolic Constituents ◽  
The Central Nervous System ◽  
Developed Nations

With an increase in the longevity and thus the proportion of the elderly, especially in developed nations, there is a rise in pathological conditions that accompany ageing, such as neurodegenerative disorders. Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive and memory decline. The pathophysiology of the disease is poorly understood, with several factors contributing to its development, such as oxidative stress, neuroinflammation, cholinergic neuronal apoptotic death, and the accumulation of abnormal proteins in the brain. Current medications are only palliative and cannot stop or reverse the progression of the disease. Recent clinical trials of synthetic compounds for the treatment of AD have failed because of their adverse effects or lack of efficacy. Thus, there is impetus behind the search for drugs from natural origins, in addition to the discovery of novel, conventional therapeutics. Mints have been used traditionally for conditions relevant to the central nervous system. Recent studies showed that mint extracts and/or their phenolic constituents have a neuroprotective potential and can target multiple events of AD. In this review, we provide evidence of the potential role of mint extracts and their derivatives as possible sources of treatments in managing AD. Some of the molecular pathways implicated in the development of AD are reviewed, with focus on apoptosis and some redox pathways, pointing to mechanisms that may be modulated for the treatment of AD, and the need for future research invoking knowledge of these pathways is highlighted.

The role of ubiquitin proteasomal system and autophagy-lysosome pathway in Alzheimer’s disease

2017 ◽  
Vol 28 (8) ◽  
Author(s):  
Yuan Zhang ◽  
Xu Chen ◽  
Yanfang Zhao ◽  
Murugavel Ponnusamy ◽  
Ying Liu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Degradation ◽  
Molecular Chaperones ◽  
Elderly Population ◽  
Neurodegenerative Disorder ◽  
The Elderly ◽  
Pathological Process ◽  
Β Amyloid

AbstractAlzheimer’s disease (AD) is the most common neurodegenerative disorder leading to dementia in the elderly population. AD is associated with the buildup of β-amyloid and tau, which aggregate into extracellular plaques and neurofibrillary tangles. Although the exact mechanism of pathological process of AD is unclear, the dysfunction of protein degradation mechanisms has been proposed to play an important role in AD. The cellular degradation of abnormal or misfolded proteins consists of three different mechanisms: the ubiquitin proteasomal system (UPS), autophagy-lysosomal pathway (ALP), and interaction of molecular chaperones with UPS or ALP. Any disturbance to these systems causes proteins to accumulate, resulting in pathological process of AD. In this review, we summarize the knowledge of protein degradation pathways in the pathogenesis of AD in light of the current literature. In the future, the regulation UPS or ALP machineries could be the cornerstones of the treatment of AD.

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