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.

Nitrosative Stress, Cellular Stress Response, and Thiol Homeostasis in Patients with Alzheimer's Disease

2006 ◽  
Vol 8 (11-12) ◽  
pp. 1975-1986 ◽  
Author(s):  
Vittorio Calabrese ◽  
Rukhsana Sultana ◽  
Giovanni Scapagnini ◽  
Eleonora Guagliano ◽  
Maria Sapienza ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stress Response ◽  
Nitrosative Stress ◽  
Cellular Stress ◽  
Cellular Stress Response ◽  
Thiol Homeostasis

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.

scholarly journals Microglial Progranulin: Involvement in Alzheimer’s Disease and Neurodegenerative Diseases

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 230 ◽  
Author(s):  
Anarmaa Mendsaikhan ◽  
Ikuo Tooyama ◽  
Douglas G. Walker
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Experimental Models ◽  
Lysosomal Storage ◽  
Cellular Functions ◽  
New Treatments ◽  
Regulatory Properties ◽  
Microglial Inflammation

Neurodegenerative diseases such as Alzheimer’s disease have proven resistant to new treatments. The complexity of neurodegenerative disease mechanisms can be highlighted by accumulating evidence for a role for a growth factor, progranulin (PGRN). PGRN is a glycoprotein encoded by the GRN/Grn gene with multiple cellular functions, including neurotrophic, anti-inflammatory and lysosome regulatory properties. Mutations in the GRN gene can lead to frontotemporal lobar degeneration (FTLD), a cause of dementia, and neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. Both diseases are associated with loss of PGRN function resulting, amongst other features, in enhanced microglial neuroinflammation and lysosomal dysfunction. PGRN has also been implicated in Alzheimer’s disease (AD). Unlike FTLD, increased expression of PGRN occurs in brains of human AD cases and AD model mice, particularly in activated microglia. How microglial PGRN might be involved in AD and other neurodegenerative diseases will be discussed. A unifying feature of PGRN in diseases might be its modulation of lysosomal function in neurons and microglia. Many experimental models have focused on consequences of PGRN gene deletion: however, possible outcomes of increasing PGRN on microglial inflammation and neurodegeneration will be discussed. We will also suggest directions for future studies on PGRN and microglia in relation to neurodegenerative diseases.

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

SIRT1 as a therapeutic target for Alzheimer’s disease

2016 ◽  
Vol 27 (8) ◽  
pp. 813-825 ◽  
Author(s):  
Siew Ying Wong ◽  
Bor Luen Tang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transcription Factors ◽  
Stress Response ◽  
Energy Metabolism ◽  
Cellular Senescence ◽  
Therapeutic Target ◽  
Disease Onset ◽  
Mechanisms Of Action ◽  
Neuron Function

AbstractAlzheimer’s disease (AD) is the most prevalent cause of dementia in the aging population worldwide. SIRT1 deacetylation of histones and transcription factors impinge on multiple neuronal and non-neuronal targets, and modulates stress response, energy metabolism and cellular senescence/death pathways. Collectively, SIRT1 activity could potentially affect multiple aspects of hippocampal and cortical neuron function and survival, thus modifying disease onset and progression. In this review, the known and potential mechanisms of action of SIRT1 with regard to AD, and its potential as a therapeutic target, are discussed.

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