Dataset Information

Decoding the Role of Platelets and Related MicroRNAs in Aging and Neurodegenerative Disorders.

ABSTRACT: Platelets are anucleate cells that circulate in blood and are essential components of the hemostatic system. During aging, platelet numbers decrease and their aggregation capacity is reduced. Platelet dysfunctions associated with aging can be linked to molecular alterations affecting several cellular systems that include cytoskeleton rearrangements, signal transduction, vesicular trafficking, and protein degradation. Age platelets may adopt a phenotype characterized by robust secretion of extracellular vesicles that could in turn account for about 70-90% of blood circulating vesicles. Interestingly these extracellular vesicles are loaded with messenger RNAs and microRNAs that may have a profound impact on protein physiology at the systems level. Age platelet dysfunction is also associated with accumulation of reactive oxygen species. Thereby understanding the mechanisms of aging in platelets as well as their age-dependent dysfunctions may be of interest when evaluating the contribution of aging to the onset of age-dependent pathologies, such as those affecting the nervous system. In this review we summarize the findings that link platelet dysfunctions to neurodegenerative diseases including Alzheimer's Disease, Parkinson's Disease, Multiple Sclerosis, Huntington's Disease, and Amyotrophic Lateral Sclerosis. We discuss the role of platelets as drivers of protein dysfunctions observed in these pathologies, their association with aging and the potential clinical significance of platelets, and related miRNAs, as peripheral biomarkers for diagnosis and prognosis of neurodegenerative diseases.

SUBMITTER: Espinosa-Parrilla Y

PROVIDER: S-EPMC6614495 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Decoding the Role of Platelets and Related MicroRNAs in Aging and Neurodegenerative Disorders.

Espinosa-Parrilla Yolanda Y Gonzalez-Billault Christian C Fuentes Eduardo E Palomo Ivan I Alarcón Marcelo M

Frontiers in aging neuroscience 20190702

Platelets are anucleate cells that circulate in blood and are essential components of the hemostatic system. During aging, platelet numbers decrease and their aggregation capacity is reduced. Platelet dysfunctions associated with aging can be linked to molecular alterations affecting several cellular systems that include cytoskeleton rearrangements, signal transduction, vesicular trafficking, and protein degradation. Age platelets may adopt a phenotype characterized by robust secretion of extrac ...[more]

PMID: 31312134

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Project description:ImportancePosttraumatic stress disorder (PTSD) has been associated with increased risk for dementia. Less is known, however, about other stress-related disorders and their associations with neurodegenerative diseases.ObjectiveTo examine the association between stress-related disorders and risk for neurodegenerative diseases.Design, setting, and participantsThis population-matched and sibling cohort study was conducted in Sweden using data from nationwide health registers, including the Swedish National Patient Register. Individuals who received their first diagnosis of stress-related disorders between January 1, 1987, and December 31, 2008, were identified. Individuals who had a history of neurodegenerative diseases, had conflicting or missing information, had no data on family links, or were aged 40 years or younger at the end of the study were excluded. Individuals with stress-related disorders were compared with the general population in a matched cohort design; they were also compared with their siblings in a sibling cohort. Follow-up commenced from the age of 40 years or 5 years after the diagnosis of stress-related disorders, whichever came later, until the first diagnosis of a neurodegenerative disease, death, emigration, or the end of follow-up (December 31, 2013), whichever occurred first. Data analyses were performed from November 2018 to April 2019.ExposuresDiagnosis of stress-related disorders (PTSD, acute stress reaction, adjustment disorder, and other stress reactions).Main outcomes and measurementsNeurodegenerative diseases were identified through the National Patient Register and classified as primary or vascular. Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis were evaluated separately. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% CIs after controlling for multiple confounders.ResultsThe population-matched cohort included 61 748 exposed individuals and 595 335 matched unexposed individuals. A total of 44 839 exposed individuals and their 78 482 unaffected full siblings were included in the sibling cohort analysis. The median (interquartile range) age at the start of follow-up was 47 (41-56) years, and 24 323 (39.4%) of the exposed individuals were male. The median (interquartile range) follow-up was 4.7 (2.1-9.8) years. Compared with unexposed individuals, individuals with a stress-related disorder were at an increased risk of neurodegenerative diseases (HR, 1.57; 95% CI, 1.43-1.73). The risk increase was greater for vascular neurodegenerative diseases (HR, 1.80; 95% CI, 1.40-2.31) than for primary neurodegenerative diseases (HR, 1.31; 95% CI, 1.15-1.48). A statistically significant association was found for Alzheimer disease (HR, 1.36; 95% CI, 1.12-1.67) but not Parkinson disease (HR, 1.20; 95% CI, 0.98-1.47) or amyotrophic lateral sclerosis (HR, 1.20; 95% CI, 0.74-1.96). Results from the sibling cohort corroborated results from the population-matched cohort.Conclusions and relevanceThis study showed an association between stress-related disorders and an increased risk of neurodegenerative diseases. The relative strength of this association for vascular neurodegenerative diseases suggests a potential cerebrovascular pathway.

Dataset Information

Decoding the Role of Platelets and Related MicroRNAs in Aging and Neurodegenerative Disorders.

Publications

Decoding the Role of Platelets and Related MicroRNAs in Aging and Neurodegenerative Disorders.

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