scholarly journals The Role of Mitochondria in Alzheimer’s Disease and its Potential Therapies

2020 ◽  
pp. 175-183
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Abilities ◽  
Metabolic Pathways ◽  
Elderly Population ◽  
The Elderly ◽  
Gradual Decline ◽  
Potential Therapeutic Target ◽  
Diet And Lifestyle

Alzheimer’s disease (AD) is a common form of dementia, affecting millions of people worldwide, mostly the elderly population. The gradual decline in cognitive functions, loss of memory, and sleep disorder are the most frequently reported in AD patients. Multiple studies have been carried out to find a potential therapeutic approach to prevent the progression of Alzheimer’s disease and increase the performance of cognitive abilities. Mitochondrial dysfunction leading to oxidative stress and other environmental factors, diet and lifestyle are the major risk factors. Mitochondria play an essential role and are a potential therapeutic target for treating and preventing AD progression. Various biochemical molecules involved in mitochondrial metabolic pathways are tested as directly acting on mitochondria. Numerous antioxidants are considered as a potential treatment for AD. Here, we highlighted the emerging mitochondrial base therapies and potent antioxidants that can be used in Alzheimer’s disease treatments.

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.

scholarly journals The Role of Aβ in the Development of Alzheimer’s Disease and its Mechanisms

2020 ◽  
Vol 218 ◽  
pp. 03041
Author(s):  
Yifei Jin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Elderly Population ◽  
Clinical Symptoms ◽  
Senile Plaques ◽  
The Elderly ◽  
Aβ Peptides ◽  
Hyperphosphorylated Tau Protein ◽  
Neurodegenerative Dementia

Alzheimer’s disease (AD) is chronic neurodegenerative dementia representing the most common cause of dementia in the elderly population. It is a major source of morbidity, mortality, and healthcare expenditure worldwide. Although the molecular and cellular properties related to AD have been demonstrated decades before the onset of clinical symptoms, AD’s pathogenesis is still unknown as a combination of risk factors causes it. Today, pathogenesis theories focused on senile plaques (SP) formed by the extracellular accumulation and deposition of Aβ peptides and neurofibrillary tangles (NFTs), which are composed of the hyperphosphorylated tau protein. Furthermore, growing evidence points out that toxic Aβ plays a primary causal role in the induction and transmission of pathology and neuronal dysfunction and loss. Therefore, Aβ is crucial to the development of AD and is a noteworthy issue in AD research. This review shows the formation of Aβ and the differences of cytotoxicity of its various isoforms and aggregation states. It also summarizes the mechanisms by which Aβ induce AD through its neurotoxicity and state how these mechanisms interact and reinforce each other.

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.

scholarly journals APOE-ε4 polymorphism and cognitive deficit among the elderly population of Fernando de Noronha

2008 ◽  
Vol 66 (2b) ◽  
pp. 298-302 ◽  
Author(s):  
Anália Nusya Garcia ◽  
Helker Albuquerque da Silva ◽  
Renan Carlos Silva ◽  
Eliane Maria Medeiros Leal ◽  
Lorena Rodrigues ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Elderly Population ◽  
Cognitive Deficit ◽  
The Elderly ◽  
Clock Drawing Test ◽  
Apoe Ε4 ◽  
Pcr Rflp ◽  
Fernando De Noronha ◽  
Ε4 Allele

BACKGROUND: Polymorphism of the gene for apolipoprotein E (APOE) is an important risk factor for the development of Alzheimer's disease. The ε4 allele of the APOE gene has been linked with a number of neuropsychiatric illnesses, and also with stress and depression among geriatric populations. OBJECTIVE: To identify APOE-ε4 polymorphism and correlate this with cognitive deficit among the elderly population of the island of Fernando de Noronha. METHOD: Neuropsychiatric tests (mini-mental state examination, verbal fluency test and clock drawing test) were applied to 52 elderly people without Alzheimer's disease. DNA was isolated from peripheral blood and genotyping of APOE was done by the PCR-RFLP method. RESULTS: 87% of the elderly population (mean age 69.6±7.0) had cognitive deficit. CONCLUSION: The observed frequency of the ε4 allele was 10%, but the correlation between the presence of ε4 and cognitive deficit in this population was not statistically significant.

scholarly journals The Prevalence of Alzheimer’s Disease; its Risk and Protective Factors Among the Elderly Population in Iran

2017 ◽  
Vol 18 (9) ◽  
Author(s):  
Sakineh Gholamzadeh ◽  
Banafsheh Heshmati ◽  
Arash Mani ◽  
Peyman Petramfar ◽  
Zahra Baghery
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protective Factors ◽  
Elderly Population ◽  
The Elderly ◽  
Risk And Protective Factors

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.

Metabolomic Alterations in the Blood and Brain in Association with Alzheimer’s Disease: Evidence from in vivo to Clinical Studies

2021 ◽  
pp. 1-28
Author(s):  
Sirawit Sriwichaiin ◽  
Nipon Chattipakorn ◽  
Siriporn C. Chattipakorn
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Studies ◽  
Elderly Population ◽  
The Elderly ◽  
Pathological Findings ◽  
Major Health Problem ◽  
Major Health ◽  
The Brain

Alzheimer’s disease (AD) has become a major health problem among the elderly population. Some evidence suggests that metabolic disturbance possibly plays a role in the pathophysiology of AD. Currently, the study of metabolomics has been used to explore changes in multiple metabolites in several diseases, including AD. Thus, the metabolomics research in AD might provide some information regarding metabolic dysregulations, and their possible associated pathophysiology. This review summarizes the information discovered regarding the metabolites in the brain and the blood from the metabolomics research of AD from both animal and clinical studies. Additionally, the correlation between the changes in metabolites and outcomes, such as pathological findings in the brain and cognitive impairment are discussed. We also deliberate on the findings of cohort studies, demonstrating the alterations in metabolites before changes of cognitive function. All of these findings can be used to inform the potential identity of specific metabolites as possible biomarkers for AD.

scholarly journals The bile acid TUDCA improves glucose homeostasis through increase of insulin levels in mice with Alzheimer's disease

2019 ◽  
Author(s):  
Lucas Zangerolamo ◽  
Helena Cristina de Lima Barbosa Sampaio ◽  
Jean Franciesco Vettorazzi ◽  
Carina Solon ◽  
Gabriela Moreira Soares ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Bile Acid ◽  
Elderly Population ◽  
Population Studies ◽  
The Elderly ◽  
Insulin Homeostasis ◽  
Aβ Oligomer

Alzheimer's disease (AD) and Type 2 Diabetes Mellitus (T2DM) are two of the most prevalent disorders in the elderly population. Studies suggest that people with T2DM have higher risk of developing AD. Likewise, AD brains presents Insulin resistance resulting in low capacity of glucose uptake. There is a growing evidence that insulin resistance and downstream abnormalities in the insulin signaling pathway are present in the AD brain and contribute to the development of cognitive dysfunction. Here we reported that C57BL/6 mice submitted to intracerebroventricular injection of streptozotocin, model of AD, and treated during 10 days with the bile acid TUDCA presented reduced accumulation of Aβ oligomer in the hippocampus and higher insulin secretion and glucose tolerance, besides improvement in memory test, suggesting that TUDCA treatment interferes with glucose-insulin homeostasis in brain and consequently attenuates AD.

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