scholarly journals Protein Homeostasis Networks and the Use of Yeast to Guide Interventions in Alzheimer’s Disease

2020 ◽  
Vol 21 (21) ◽  
pp. 8014
Author(s):  
Sudip Dhakal ◽  
Ian Macreadie
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stress Responses ◽  
Cell Biology ◽  
Neurodegenerative Disorder ◽  
The Elderly ◽  
Yeast Cells ◽  
Yeast Genome ◽  
Protein Homeostasis ◽  
Age Related

Alzheimer’s Disease (AD) is a progressive multifactorial age-related neurodegenerative disorder that causes the majority of deaths due to dementia in the elderly. Although various risk factors have been found to be associated with AD progression, the cause of the disease is still unresolved. The loss of proteostasis is one of the major causes of AD: it is evident by aggregation of misfolded proteins, lipid homeostasis disruption, accumulation of autophagic vesicles, and oxidative damage during the disease progression. Different models have been developed to study AD, one of which is a yeast model. Yeasts are simple unicellular eukaryotic cells that have provided great insights into human cell biology. Various yeast models, including unmodified and genetically modified yeasts, have been established for studying AD and have provided significant amount of information on AD pathology and potential interventions. The conservation of various human biological processes, including signal transduction, energy metabolism, protein homeostasis, stress responses, oxidative phosphorylation, vesicle trafficking, apoptosis, endocytosis, and ageing, renders yeast a fascinating, powerful model for AD. In addition, the easy manipulation of the yeast genome and availability of methods to evaluate yeast cells rapidly in high throughput technological platforms strengthen the rationale of using yeast as a model. This review focuses on the description of the proteostasis network in yeast and its comparison with the human proteostasis network. It further elaborates on the AD-associated proteostasis failure and applications of the yeast proteostasis network to understand AD pathology and its potential to guide interventions against AD.

scholarly journals Curcumin and Its Derivatives as Theranostic Agents in Alzheimer’s Disease: The Implication of Nanotechnology

2020 ◽  
Vol 22 (1) ◽  
pp. 196
Author(s):  
Umair Shabbir ◽  
Momna Rubab ◽  
Akanksha Tyagi ◽  
Deog-Hwan Oh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
The Elderly ◽  
Biological Properties ◽  
Age Related ◽  
Theranostic Agents ◽  
Nutritional Compounds ◽  
Age Related Cognitive Decline ◽  
Effective Drugs

Curcumin is a polyphenolic natural compound with diverse and attractive biological properties, which may prevent or ameliorate pathological processes underlying age-related cognitive decline, Alzheimer’s disease (AD), dementia, or mode disorders. AD is a chronic neurodegenerative disorder that is known as one of the rapidly growing diseases, especially in the elderly population. Moreover, being the eminent cause of dementia, posing problems for families, societies as well a severe burden on the economy. There are no effective drugs to cure AD. Although curcumin and its derivatives have shown properties that can be considered useful in inhibiting the hallmarks of AD, however, they have low bioavailability. Furthermore, to combat diagnostic and therapeutic limitations, various nanoformulations have also been recognized as theranostic agents that can also enhance the pharmacokinetic properties of curcumin and other bioactive compounds. Nanocarriers have shown beneficial properties to deliver curcumin and other nutritional compounds against the blood-brain barrier to efficiently distribute them in the brain. This review spotlights the role and effectiveness of curcumin and its derivatives in AD. Besides, the gut metabolism of curcumin and the effects of nanoparticles and their possible activity as diagnostic and therapeutic agents in AD also discussed.

ADULT NEUROGENESIS: ALTERATIONS WITH AGING AND ALZHEIMER’S DISEASE DEVELOPMENT

2021 ◽  
pp. 1080-1087
Author(s):  
А. О. Бурняшева ◽  
Н. А. Стефанова ◽  
Е. А. Рудницкая
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adult Neurogenesis ◽  
Neurodegenerative Disorder ◽  
Brain Plasticity ◽  
The Elderly ◽  
Adult Brain ◽  
Molecular Control ◽  
Neurogenic Niche ◽  
Age Related

Нейрогенез в головном мозге взрослого организма - один из важнейших механизмов пластичности, который проявляется увеличением числа клеток, участвующих в структурной перестройке нейрональных сетей и формированием синапсов, и способствует увеличению функциональных возможностей головного мозга. С возрастом и при развитии нейродегенеративных расстройств происходит нарушение микроокружения нейрогенной ниши, ослабление контроля и, как следствие, значительное снижение нейрогенеза, что, в свою очередь, может способствовать ухудшению когнитивных способностей и развитию деменции. Наиболее распространённой сенильной деменцией является болезнь Альцгеймера - неизлечимое заболевание нейродегенеративной природы, при котором одними из первых поражаются гиппокамп и энторинальная кора - ключевые нейрогенные ниши зрелого головного мозга, что приводит к нарушению нейрогенеза и способствует дальнейшей прогрессии дегенеративных процессов. На сегодняшний день механизмы, лежащие в основе сопровождающих развитие болезни Альцгеймера изменений нейрогенеза, остаются до конца неясными и являются предметом интенсивного изучения исследователей во всём мире как потенциальная мишень для коррекции патологических изменений. Adult neurogenesis is one of the key mechanisms of the brain plasticity. Increase in the number of cells participating in the rearrangement of the neuronal circuits and synaptic formation facilitates the increase of brain’s functional capacity. However, aging as well as neurodegenerative disorders lead to the disruption of the neurogenic niche microenvironment and the loss of molecular control, which in turn results in the significant decline of the neurogenesis. These events may contribute to the cognitive decline and the consequent development of dementia. Alzheimer’s disease is a progressive incurable age-related neurodegenerative disorder in the elderly and the most prevalent cause of dementia. Hippocampus and entorhinal cortex are the key neurogenic niches in the adult brain and one of the most vulnerable brain areas during the development of Alzheimer’s disease. Thus, neurodegeneration associated with the development of Alzheimer’s disease affects adult neurogenesis. However, to date the mechanisms underlying this connection are unclear, and the investigation of these mechanisms is a promising strategy to find the approaches to correct the Alzheimer’s disease pathology.

scholarly journals The Conspicuous Link between Ear, Brain and Heart–Could Neurotrophin-Treatment of Age-Related Hearing Loss Help Prevent Alzheimer’s Disease and Associated Amyloid Cardiomyopathy?

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 900
Author(s):  
Sergey Shityakov ◽  
Kentaro Hayashi ◽  
Stefan Störk ◽  
Verena Scheper ◽  
Thomas Lenarz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Neurodegenerative Disorder ◽  
Amyloid Β ◽  
The Elderly ◽  
Amyloid Β Peptide ◽  
Age Related ◽  
Amyloid Cardiomyopathy ◽  
Age Related Hearing Loss

Alzheimer’s disease (AD), the most common cause of dementia in the elderly, is a neurodegenerative disorder associated with neurovascular dysfunction and cognitive decline. While the deposition of amyloid β peptide (Aβ) and the formation of neurofibrillary tangles (NFTs) are the pathological hallmarks of AD-affected brains, the majority of cases exhibits a combination of comorbidities that ultimately lead to multi-organ failure. Of particular interest, it can be demonstrated that Aβ pathology is present in the hearts of patients with AD, while the formation of NFT in the auditory system can be detected much earlier than the onset of symptoms. Progressive hearing impairment may beget social isolation and accelerate cognitive decline and increase the risk of developing dementia. The current review discusses the concept of a brain–ear–heart axis by which Aβ and NFT inhibition could be achieved through targeted supplementation of neurotrophic factors to the cochlea and the brain. Such amyloid inhibition might also indirectly affect amyloid accumulation in the heart, thus reducing the risk of developing AD-associated amyloid cardiomyopathy and cardiovascular disease.

Emerging Promise of Immunotherapy for Alzheimer’s Disease: A New Hope for the Development of Alzheimer’s Vaccine

2020 ◽  
Vol 20 (13) ◽  
pp. 1214-1234 ◽  
Author(s):  
Md. Tanvir Kabir ◽  
Md. Sahab Uddin ◽  
Bijo Mathew ◽  
Pankoj Kumar Das ◽  
Asma Perveen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune Response ◽  
Neutralizing Antibodies ◽  
Neurodegenerative Disorder ◽  
Symptomatic Relief ◽  
Aβ Oligomers ◽  
Th2 Immune Response ◽  
Age Related ◽  
Anti Inflammatory

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the characteristics of this devastating disorder include the progressive and disabling deficits in the cognitive functions including reasoning, attention, judgment, comprehension, memory, and language. Objective: In this article, we have focused on the recent progress that has been achieved in the development of an effective AD vaccine. Summary: Currently, available treatment options of AD are limited to deliver short-term symptomatic relief only. A number of strategies targeting amyloid-beta (Aβ) have been developed in order to treat or prevent AD. In order to exert an effective immune response, an AD vaccine should contain adjuvants that can induce an effective anti-inflammatory T helper 2 (Th2) immune response. AD vaccines should also possess the immunogens which have the capacity to stimulate a protective immune response against various cytotoxic Aβ conformers. The induction of an effective vaccine’s immune response would necessitate the parallel delivery of immunogen to dendritic cells (DCs) and their priming to stimulate a Th2-polarized response. The aforesaid immune response is likely to mediate the generation of neutralizing antibodies against the neurotoxic Aβ oligomers (AβOs) and also anti-inflammatory cytokines, thus preventing the AD-related inflammation. Conclusion: Since there is an age-related decline in the immune functions, therefore vaccines are more likely to prevent AD instead of providing treatment. AD vaccines might be an effective and convenient approach to avoid the treatment-related huge expense.

scholarly journals Immunosenescence of Natural Killer Cells, Inflammation, and Alzheimer’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Corona Solana ◽  
Raquel Tarazona ◽  
Rafael Solana
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Neurodegenerative Disorder ◽  
The Elderly ◽  
Lymphoid Cells ◽  
Target Cells ◽  
The Brain

Alzheimer’s disease (AD) represents the most common cause of dementia in the elderly. AD is a neurodegenerative disorder characterized by progressive memory loss and cognitive decline. Although the aetiology of AD is not clear, both environmental factors and heritable predisposition may contribute to disease occurrence. In addition, inflammation and immune system alterations have been linked to AD. The prevailing hypothesis as cause of AD is the deposition in the brain of amyloid beta peptides (Aβ). Although Aβ have a role in defending the brain against infections, their accumulation promotes an inflammatory response mediated by microglia and astrocytes. The production of proinflammatory cytokines and other inflammatory mediators such as prostaglandins and complement factors favours the recruitment of peripheral immune cells further promoting neuroinflammation. Age-related inflammation and chronic infection with herpes virus such as cytomegalovirus may also contribute to inflammation in AD patients. Natural killer (NK) cells are innate lymphoid cells involved in host defence against viral infections and tumours. Once activated NK cells secrete cytokines such as IFN-γ and TNF-α and chemokines and exert cytotoxic activity against target cells. In the elderly, changes in NK cell compartment have been described which may contribute to the lower capacity of elderly individuals to respond to pathogens and tumours. Recently, the role of NK cells in the immunopathogenesis of AD is discussed. Although in AD patients the frequency of NK cells is not affected, a high NK cell response to cytokines has been described together with NK cell dysregulation of signalling pathways which is in part involved in this altered behaviour.

scholarly journals Good rate of clinical response to cholinesterase inhibitors in mild and moderate Alzheimer's disease after three months of treatment: An open-label study

2013 ◽  
Vol 7 (2) ◽  
pp. 190-196 ◽  
Author(s):  
Luis Felipe José Ravic de Miranda ◽  
Marilourdes do Amaral Barbosa ◽  
Patrícia Regina Henrique Peles ◽  
Patrícia Hilar Pôças ◽  
Pedro Augusto Lopes Tito ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrovascular Disease ◽  
Clinical Response ◽  
Cholinesterase Inhibitors ◽  
Rating Scale ◽  
The Elderly ◽  
Open Label ◽  
Age Related ◽  
Moderate Dementia

ABSTRACT Life expectancy in Brazil has increased markedly over the last 30 years. Hence, age-related disorders, such as Alzheimer's disease (AD), warrant special attention due to their high prevalence in the elderly. Pharmacologic treatment of AD is based on cholinesterase inhibitors (ChEI) and memantine, leading to modest clinical benefits both in the short and long-term. However, clinical response is heterogeneous and needs further investigation. Objective: To investigate the rate of response to ChEI in AD after three months of treatment. Methods: Patients with mild or moderate dementia due to probable AD or to AD associated with cerebrovascular disease were included in the study. The subjects were assessed at baseline and again after three months of ChEI treatment. Subjects were submitted to the Mini-Mental State Examination (MMSE), Mattis Dementia Rating Scale, Katz Basic Activities of Daily Living, Pfeffer Functional Activities Questionnaire, Neuropsychiatric Inventory and Cornell Scale for Depression in Dementia. Good response was defined by a gain of ≥2 points on the MMSE after three months of treatment in relation to baseline. Results: Seventy-one patients, 66 (93%) with probable AD and five (7%) with AD associated with cerebrovascular disease, were evaluated. The good response rate at three months was 31.0%, being 37.2% and 21.4% in mild and moderate dementia, respectively. There were no significant differences on most tests, except for improvement in hallucinations, agitation and dysphoria in moderate dementia patients. Conclusion: The rate of good clinical response to ChEI was higher than usually reported. Specific behavioral features significantly improved in the subgroup of moderate dementia.

Preventing Alzheimer's Wandering

2019 ◽  
pp. 77-89
Author(s):  
Sara Paiva ◽  
Rui Peleja ◽  
Jorge Cunha ◽  
Carlos Abreu
Keyword(s):  
Quality Of Life ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Quality Of Care ◽  
Cognitive Impairments ◽  
The Elderly ◽  
Strong Impact ◽  
Brain Disorder ◽  
Age Related

With increased life expectancy, the incidence of age-related cognitive impairments, faced by the elderly and older generations, is growing. Among the population with cognitive impairments, those that suffer from Alzheimer's disease are the most common. The Alzheimer's disease is a chronic degenerative brain disorder that is characterised by a failure of memory and, in some instances, by disorders in language, perception and planning. As a consequence of the progressive damages imposed by the illness, patients will increasingly seek and need assistance. This paper presents a tool to aid the development and managing of caregiving communities, comprising immediate family members, relatives, neighbours and healthcare professionals, to assist patients with Alzheimer's disease. Such communities could have a strong impact on the quality of care provided to the patients. At the same time, it is hoped that involving communities will significantly improve the quality of life of Alzheimer's patients and their families while reducing the costs related to the care provided.

scholarly journals Relationship between Wine Consumption, Diet and Microbiome Modulation in Alzheimer’s Disease

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3082
Author(s):  
M. Victoria Moreno-Arribas ◽  
Begoña Bartolomé ◽  
José L. Peñalvo ◽  
Patricia Pérez-Matute ◽  
Maria José Motilva
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Neurodegenerative Disorder ◽  
Current Knowledge ◽  
Intestinal Microbiome ◽  
Dietary Polyphenols ◽  
Age Related ◽  
Wine Polyphenols ◽  
The Impact

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder leading to the most common form of dementia in elderly people. Modifiable dietary and lifestyle factors could either accelerate or ameliorate the aging process and the risk of developing AD and other age-related morbidities. Emerging evidence also reports a potential link between oral and gut microbiota alterations and AD. Dietary polyphenols, in particular wine polyphenols, are a major diver of oral and gut microbiota composition and function. Consequently, wine polyphenols health effects, mediated as a function of the individual’s oral and gut microbiome are considered one of the recent greatest challenges in the field of neurodegenerative diseases as a promising strategy to prevent or slow down AD progression. This review highlights current knowledge on the link of oral and intestinal microbiome and the interaction between wine polyphenols and microbiota in the context of AD. Furthermore, the extent to which mechanisms bacteria and polyphenols and its microbial metabolites exert their action on communication pathways between the brain and the microbiota, as well as the impact of the molecular mediators to these interactions on AD patients, are described.

scholarly journals Repositioning of Immunomodulators: A Ray of Hope for Alzheimer’s Disease?

2020 ◽  
Vol 14 ◽  
Author(s):  
Antonio Munafò ◽  
Chiara Burgaletto ◽  
Giulia Di Benedetto ◽  
Marco Di Mauro ◽  
Rosaria Di Mauro ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Neurodegenerative Disorder ◽  
Drug Repositioning ◽  
Amyloid Β ◽  
Deep Understanding ◽  
Current Status ◽  
Age Related ◽  
Tnf Α

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder characterized by cognitive decline and by the presence of amyloid β plaques and neurofibrillary tangles in the brain. Despite recent advances in understanding its pathophysiological mechanisms, to date, there are no disease-modifying therapeutic options, to slow or halt the evolution of neurodegenerative processes in AD. Current pharmacological treatments only transiently mitigate the severity of symptoms, with modest or null overall improvement. Emerging evidence supports the concept that AD is affected by the impaired ability of the immune system to restrain the brain’s pathology. Deep understanding of the relationship between the nervous and the immune system may provide a novel arena to develop effective and safe drugs for AD treatment. Considering the crucial role of inflammatory/immune pathways in AD, here we discuss the current status of the immuno-oncological, immunomodulatory and anti-TNF-α drugs which are being used in preclinical studies or in ongoing clinical trials by means of the drug-repositioning approach.

scholarly journals Tau induces blood vessel abnormalities and angiogenesis-related gene expression in P301L transgenic mice and human Alzheimer’s disease

2018 ◽  
Vol 115 (6) ◽  
pp. E1289-E1298 ◽  
Author(s):  
Rachel E. Bennett ◽  
Ashley B. Robbins ◽  
Miwei Hu ◽  
Xinrui Cao ◽  
Rebecca A. Betensky ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Flow ◽  
Blood Vessel ◽  
Cell Biology ◽  
The Elderly ◽  
Brain Regions ◽  
Cortical Atrophy ◽  
Vascular Abnormalities ◽  
Alzheimer Pathology

Mixed pathology, with both Alzheimer’s disease and vascular abnormalities, is the most common cause of clinical dementia in the elderly. While usually thought to be concurrent diseases, the fact that changes in cerebral blood flow are a prominent early and persistent alteration in Alzheimer’s disease raises the possibility that vascular alterations and Alzheimer pathology are more directly linked. Here, we report that aged tau-overexpressing mice develop changes to blood vessels including abnormal, spiraling morphologies; reduced blood vessel diameters; and increased overall blood vessel density in cortex. Blood flow in these vessels was altered, with periods of obstructed flow rarely observed in normal capillaries. These changes were accompanied by cortical atrophy as well as increased expression of angiogenesis-related genes such as Vegfa, Serpine1, and Plau in CD31-positive endothelial cells. Interestingly, mice overexpressing nonmutant forms of tau in the absence of frank neurodegeneration also demonstrated similar changes. Furthermore, many of the genes we observe in mice are also altered in human RNA datasets from Alzheimer patients, particularly in brain regions classically associated with tau pathology such as the temporal lobe and limbic system regions. Together these data indicate that tau pathological changes in neurons can impact brain endothelial cell biology, altering the integrity of the brain’s microvasculature.

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