Alteration of the Neurofilament-Microtubule Network in Alzheimer Disease and Other Neurodegenerative Disorders

Author(s):  
George Perry ◽  
Valeria Manetto ◽  
Michelle Onorato ◽  
Madelyn Weiss ◽  
Paul Mulvihill ◽  
...  
2020 ◽  
Vol 10 (11) ◽  
pp. 862
Author(s):  
Stéphanie Papin ◽  
Paolo Paganetti

Neurodegenerative disorders and cancer may appear unrelated illnesses. Yet, epidemiologic studies indicate an inverse correlation between their respective incidences for specific cancers. Possibly explaining these findings, increasing evidence indicates that common molecular pathways are involved, often in opposite manner, in the pathogenesis of both disease families. Genetic mutations in the MAPT gene encoding for TAU protein cause an inherited form of frontotemporal dementia, a neurodegenerative disorder, but also increase the risk of developing cancer. Assigning TAU at the interface between cancer and neurodegenerative disorders, two major aging-linked disease families, offers a possible clue for the epidemiological observation inversely correlating these human illnesses. In addition, the expression level of TAU is recognized as a prognostic marker for cancer, as well as a modifier of cancer resistance to chemotherapy. Because of its microtubule-binding properties, TAU may interfere with the mechanism of action of taxanes, a class of chemotherapeutic drugs designed to stabilize the microtubule network and impair cell division. Indeed, a low TAU expression is associated to a better response to taxanes. Although TAU main binding partners are microtubules, TAU is able to relocate to subcellular sites devoid of microtubules and is also able to bind to cancer-linked proteins, suggesting a role of TAU in modulating microtubule-independent cellular pathways associated to oncogenesis. This concept is strengthened by experimental evidence linking TAU to P53 signaling, DNA stability and protection, processes that protect against cancer. This review aims at collecting literature data supporting the association between TAU and cancer. We will first summarize the evidence linking neurodegenerative disorders and cancer, then published data supporting a role of TAU as a modifier of the efficacy of chemotherapies and of the oncogenic process. We will finish by addressing from a mechanistic point of view the role of TAU in de-regulating critical cancer pathways, including the interaction of TAU with cancer-associated proteins.


1997 ◽  
Vol 3 (2) ◽  
pp. 181-206 ◽  
Author(s):  
Antön Alvarez ◽  
José J. Miguel-Hidalgo ◽  
Lucía Fernandez-Novoa ◽  
Joaquín Díaz ◽  
José M. Sempere ◽  
...  

2020 ◽  
Vol 11 (5) ◽  
pp. 1161-1173
Author(s):  
Janett Barbaresko ◽  
Arno Werner Lellmann ◽  
Annemarie Schmidt ◽  
Andreas Lehmann ◽  
Anna Maria Amini ◽  
...  

ABSTRACT Diet has been hypothesized to be associated with neurodegenerative disorders. The aim was to conduct an umbrella review to summarize and evaluate the current evidence of prospective associations between any dietary factors and the incidence of neurodegenerative disorders. We conducted a systematic search in PubMed, Embase, and the Cochrane library up to November 2019 to identify systematic reviews with meta-analyses of prospective studies investigating the association between dietary factors (dietary patterns, foods and beverages, nutrients, and phytochemicals) and neurodegenerative disorders (cognitive decline, cognitive impairment, Alzheimer disease, all-cause dementia, and Parkinson disease). Summary risk ratios (SRRs) and 95% CIs were recalculated using a random effects model. We evaluated the risk of bias of identified meta-analyses and the quality of evidence for all associations. In total, 20 meta-analyses including 98 SRRs were identified. All original meta-analyses were rated as being at high risk of bias. Methodological concerns related mainly to the inappropriate synthesis, assessment, and discussion of the risk of bias of primary studies. For the recalculated meta-analyses, quality of evidence was moderate for inverse associations between higher adherence to the Mediterranean diet (SRR: 0.63; 95% CI: 0.48, 0.82; n = 4 primary studies) and higher fish intake (SRR: 0.72; 95% CI: 0.59, 0.89; n = 6) and Alzheimer disease, as well as for tea consumption and all-cause dementia (SRR: 0.74; 95% CI: 0.63, 0.88; n = 2) and Parkinson disease (SRR per 2 cups/d: 0.69; 95% CI: 0.54, 0.87; n = 5). This umbrella review provides a comprehensive overview of the available evidence on dietary factors and neurodegenerative disorders. The results indicate that the Mediterranean diet, fish, and tea could be inversely associated with neurodegenerative disorders. However, the quality of evidence was generally low, suggesting that further studies are likely to change the overall estimates. Thus, more well-conducted research, also investigating other dietary factors in association with neurodegenerative disorders, is warranted.


JAMA ◽  
2020 ◽  
Vol 324 (8) ◽  
pp. 772 ◽  
Author(s):  
Sebastian Palmqvist ◽  
Shorena Janelidze ◽  
Yakeel T. Quiroz ◽  
Henrik Zetterberg ◽  
Francisco Lopera ◽  
...  

2010 ◽  
Vol 28 (1) ◽  
pp. 117-133 ◽  
Author(s):  
Norm O'Rourke ◽  
Amy Claxton ◽  
Anthony L. Kupferschmidt ◽  
JuliAnna Z. Smith ◽  
B. Lynn Beattie

Few disease processes affect the dynamics of marital relationships like neurodegenerative disorders. Illnesses such as Alzheimer disease strip older adults of a lifetime of memories and, in the latter stages, even the ability to recognize one’s spouse and children. In cross-sectional research, marital idealization (or the propensity to idealize one’s spouse and relationship) has emerged as significantly associated with the absence of distress among those caring for a spouse with Alzheimer disease. To extend prior findings, multilevel models were computed for the current study to demonstrate that marital idealization predicts both life satisfaction and the relative absence of caregiver burden one year later; moreover, change in marital idealization reflects a corresponding change in the psychological well-being of spouses over this same period ( N = 90). Results of this study are discussed relative to the distinct demands of caring for a spouse with a dementing disorder, the health benefits of positive illusions, and demographic trends suggesting that family caregiving will become increasingly prevalent in coming years.


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