Unraveling the biological mechanisms in Alzheimer's disease — Lessons from genomics

2011 ◽  
Vol 35 (2) ◽  
pp. 340-347 ◽  
Author(s):  
Fran Borovecki ◽  
Natasa Klepac ◽  
Dorotea Muck-Seler ◽  
Sanja Hajnsek ◽  
Zdenko Mubrin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Biological Mechanisms

scholarly journals Inverse Correlation Between Alzheimer’s Disease and Cancer: Short Overview

2021 ◽  
Author(s):  
Agnieszka Zabłocka ◽  
Wioletta Kazana ◽  
Marta Sochocka ◽  
Bartłomiej Stańczykiewicz ◽  
Maria Janusz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Kinase Inhibitor ◽  
Fungal Infections ◽  
Neurological Diseases ◽  
Inverse Correlation ◽  
Biological Mechanisms ◽  
Age Related ◽  
Common Risk Factors

AbstractThe negative association between Alzheimer’s disease (AD) and cancer suggests that susceptibility to one disease may protect against the other. When biological mechanisms of AD and cancer and relationship between them are understood, the unsolved problem of both diseases which still touches the growing human population could be overcome. Actual information about biological mechanisms and common risk factors such as chronic inflammation, age-related metabolic deregulation, and family history is presented here. Common signaling pathways, e.g., p53, Wnt, role of Pin1, and microRNA, are discussed as well. Much attention is also paid to the potential impact of chronic viral, bacterial, and fungal infections that are responsible for the inflammatory pathway in AD and also play a key role to cancer development. New data about common mechanisms in etiopathology of cancer and neurological diseases suggests new therapeutic strategies. Among them, the use of nilotinib, tyrosine kinase inhibitor, protein kinase C, and bexarotene is the most promising.

Evidence for nucleolar dysfunction in Alzheimer’s disease

2019 ◽  
Vol 30 (7) ◽  
pp. 685-700 ◽  
Author(s):  
Caitlin Nyhus ◽  
Maria Pihl ◽  
Poul Hyttel ◽  
Vanessa Jane Hall
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stress Response ◽  
Ribosome Biogenesis ◽  
Protein Translation ◽  
Biological Mechanisms ◽  
Cellular Functions ◽  
Nucleolar Proteins ◽  
Nucleolar Stress ◽  
Nucleolar Volume

Abstract The nucleolus is a dynamically changing organelle that is central to a number of important cellular functions. Not only is it important for ribosome biogenesis, but it also reacts to stress by instigating a nucleolar stress response and is further involved in regulating the cell cycle. Several studies report nucleolar dysfunction in Alzheimer’s disease (AD). Studies have reported a decrease in both total nucleolar volume and transcriptional activity of the nucleolar organizing regions. Ribosomes appear to be targeted by oxidation and reduced protein translation has been reported. In addition, several nucleolar proteins are dysregulated and some of these appear to be implicated in classical AD pathology. Some studies also suggest that the nucleolar stress response may be activated in AD, albeit this latter research is rather limited and requires further investigation. The purpose of this review is to draw the connections of all these studies together and signify that there are clear changes in the nucleolus and the ribosomes in AD. The nucleolus is therefore an organelle that requires more attention than previously given in relation to understanding the biological mechanisms underlying the disease.

Serotoninergic antidepressants positively affect platelet ADAM10 expression in patients with Alzheimer's disease

2015 ◽  
Vol 28 (6) ◽  
pp. 939-944 ◽  
Author(s):  
Otávio Augusto Fernandes Marques Bianco ◽  
Patrícia Regina Manzine ◽  
Carla Manuela Crispim Nascimento ◽  
Francisco Assis Carvalho Vale ◽  
Sofia Cristina Iost Pavarini ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Protein Extraction ◽  
Biological Mechanisms ◽  
Important Advance ◽  
Positive Effects ◽  
Tetracyclic Antidepressants ◽  
Adam10 Expression ◽  
The Central Nervous System

ABSTRACTBackground:Studies have demonstrated a decreased platelet ADAM10 expression in patients with Alzheimer's Disease (AD), classifying this protein as a blood-based AD biomarker. About 50% of the patients with AD are diagnosed with depression, which is commonly treated with tricyclic and tetracyclic antidepressants, monoaminoxidade (MAO) inhibitors and, more preferably, with selective serotonin reuptake inhibitors (SSRIs). Considering that a large proportion of patients with AD takes antidepressant medications during the course of the disease we investigated the influence of this medication on the expression of platelet ADAM10, which is considered the main α-secretase preventing beta-amyloid (βA) formation.Methods:Blood was collected for protein extraction from platelets. ADAM10 was analyzed by using western blotting and reactive bands were measured using β-actin as endogenous control.Results:Platelet ADAM10 protein expression in patients with AD was positively influenced by serotoninergic medication.Conclusion:More studies on the positive effects of serotonergic antidepressants on ADAM10 platelet expression should be performed in order to understand its biological mechanisms and to verify whether these effects are reflected in the central nervous system. This work represents an important advance for the study of AD biomarkers, as well as for more effective pharmacological treatment of patients with AD and associated depression.

scholarly journals The acceleration of aging and Alzheimer’s disease through the biological mechanisms behind obesity and type II diabetes

Health ◽  
2013 ◽  
Vol 05 (05) ◽  
pp. 913-920 ◽  
Author(s):  
Ian James Martins ◽  
Wei Ling Florence Lim ◽  
Andrea C. Wilson ◽  
Simon M. Laws ◽  
Ralph Nigel Martins
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Type Ii Diabetes ◽  
Type Ii ◽  
Biological Mechanisms

scholarly journals Using machine intelligence to uncover Alzheimer’s disease progression heterogeneity

2020 ◽  
Vol 1 (6) ◽  
Author(s):  
Bessi Qorri ◽  
Mike Tsay ◽  
Abhishek Agrawal ◽  
Rhoda Au ◽  
Joseph Gracie
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metal Ion ◽  
Drug Repurposing ◽  
Machine Intelligence ◽  
Postmortem Brain ◽  
Class Iii ◽  
Biological Mechanisms ◽  
Data Set ◽  
Treatment Pathways

Aim: Research suggests that Alzheimer’s disease (AD) is heterogeneous with numerous subtypes. Through a proprietary interactive ML system, several underlying biological mechanisms associated with AD pathology were uncovered. This paper is an introduction to emerging analytic efforts that can more precisely elucidate the heterogeneity of AD. Methods: A public AD data set (GSE84422) consisting of transcriptomic data of postmortem brain samples from healthy controls (n = 121) and AD (n = 380) subjects was analyzed. Data were processed by an artificial intelligence platform designed to discover potential drug repurposing candidates, followed by an interactive augmented intelligence program. Results: Using perspective analytics, six perspective classes were identified: Class I is defined by TUBB1, ASB4, and PDE5A; Class II by NRG2 and ZNF3; Class III by IGF1, ASB4, and GTSE1; Class IV is defined by cDNA FLJ39269, ITGA1, and CPM; Class V is defined by PDE5A, PSEN1, and NDUFS8; and Class VI is defined by DCAF17, cDNA FLJ75819, and SLC33A1. It is hypothesized that these classes represent biological mechanisms that may act alone or in any combination to manifest an Alzheimer’s pathology. Conclusions: Using a limited transcriptomic public database, six different classes that drive AD were uncovered, supporting the premise that AD is a heterogeneously complex disorder. The perspective classes highlighted genetic pathways associated with vasculogenesis, cellular signaling and differentiation, metabolic function, mitochondrial function, nitric oxide, and metal ion metabolism. The interplay among these genetic factors reveals a more profound underlying complexity of AD that may be responsible for the confluence of several biological factors. These results are not exhaustive; instead, they demonstrate that even within a relatively small study sample, next-generation machine intelligence can uncover multiple genetically driven subtypes. The models and the underlying hypotheses generated using novel analytic methods may translate into potential treatment pathways.

Current Research on Pro-Drug Therapies for Parkinson's and Alzheimer's Disease

2021 ◽  
Vol 18 ◽  
Author(s):  
Cui Huo ◽  
Lei Wu ◽  
Zhiqiang Jiang ◽  
Jiacheng Yang ◽  
Zhouyu Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Targeted Drug Delivery ◽  
Relevant Literature ◽  
Research Progress ◽  
Design Strategies ◽  
Biological Mechanisms ◽  
Drug Bioavailability ◽  
The Central Nervous System ◽  
Approved Drugs

: Background: alzheimer's disease (ad) and parkinson's (pd) disease are common neurodegenerative conditions of the central nervous system (cns). Thus, these diseases have only been treated symptomatically since no approved drug is available that provides a complete cure. Objectives: through reading relevant literature published at home and abroad, the method and significance of prodrug strategy to increase the efficacy of ad and pd drugs were discussed. Methods: the biological mechanisms and currently approved drugs for both diseases have been discussed, revealing that most of these treatments utilized existing prodrug design strategies, including increased lipophilicity, and the use of transporters mediation and bio-oxidation to improve oral bioavailability and brain permeability. Results: the purpose of this paper is to review the research progress in the treatment of neurodegenerative diseases (ndds), especially ad and pd, using the prodrug strategy. The research of drug bioavailability and the prodrug strategy of cns targeted drug delivery lay the foundation for drug development to treat these diseases. Conclusion: the use of prodrug strategies provides important opportunities for the development of novel therapies for ad and pd.

Risk Reduction and Prevention of Alzheimer's Disease: Biological Mechanisms of Diet

2020 ◽  
Vol 17 (5) ◽  
pp. 407-427
Author(s):  
Hugo McGurran ◽  
Jordan Glenn ◽  
Erica Madero ◽  
Nick Bott
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dietary Pattern ◽  
Omega 3 ◽  
Biological Mechanisms ◽  
Beneficial Effects ◽  
Preventative Measures ◽  
Disease Modifying Agents ◽  
Risk Reducing

: Alzheimer’s Disease (AD) incidence is increasing and with no disease modifying agents available, preventative measures through lifestyle factors are being investigated. Combined with the prevention of AD risk factors such as heart disease, diabetes, and with more recent evidence, microbiome dysfunction, there is a substantial foundation for diet as a modifiable risk factor and preventative measure for AD. Recent evidence suggests AD associated pathologies, such as oxidative stress and inflammation, can be modulated by the lipids, vitamins, and polyphenols obtained through nutritional intake. Furthermore, epidemiological and preclinical evidence has uncovered certain compounds within foods that may have beneficial effects in the prevention of AD, including omega-3 fatty acids, vitamin E, and resveratrol among others. However, clinical data examining specific compounds are often inconsistent and fail to replicate the preclinical data. On the other hand, dietary patterns such as the Mediterranean or MIND diet have shown promise in terms of clinical outcomes for patients, indicating a reductionist approach to diet is not as effective as a holistic dietary pattern. In this review, we summarize some of the biological mechanisms of key compounds in their relation to AD and how they fit into a dietary pattern that supports the role of diet as a risk reducing factor for AD.

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