Dataset Information

Epidermal Growth Factor Pathway in the Age-Related Decline of Oligodendrocyte Regeneration.

ABSTRACT: Oligodendrocytes (OLs) are specialized glial cells that myelinate CNS axons. OLs are generated throughout life from oligodendrocyte progenitor cells (OPCs) via a series of tightly controlled differentiation steps. Life-long myelination is essential for learning and to replace myelin lost in age-related pathologies such as Alzheimer's disease (AD) as well as white matter pathologies such as multiple sclerosis (MS). Notably, there is considerable myelin loss in the aging brain, which is accelerated in AD and underpins the failure of remyelination in secondary progressive MS. An important factor in age-related myelin loss is a marked decrease in the regenerative capacity of OPCs. In this review, we will contextualize recent advances in the key role of Epidermal Growth Factor (EGF) signaling in regulating multiple biological pathways in oligodendroglia that are dysregulated in aging.

SUBMITTER: Rivera AD

PROVIDER: S-EPMC8968959 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Epidermal Growth Factor Pathway in the Age-Related Decline of Oligodendrocyte Regeneration.

Rivera Andrea D AD Azim Kasum K Macchi Veronica V Porzionato Andrea A Butt Arthur M AM De Caro Raffaele R

Frontiers in cellular neuroscience 20220317

Oligodendrocytes (OLs) are specialized glial cells that myelinate CNS axons. OLs are generated throughout life from oligodendrocyte progenitor cells (OPCs) <i>via</i> a series of tightly controlled differentiation steps. Life-long myelination is essential for learning and to replace myelin lost in age-related pathologies such as Alzheimer's disease (AD) as well as white matter pathologies such as multiple sclerosis (MS). Notably, there is considerable myelin loss in the aging brain, which is acc ...[more]

PMID: 35370556

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Project description:Rationale & objectiveThe diagnosis and prognostication of chronic kidney disease (CKD) largely rely on glomerular measures that may not reflect tubular damage. We investigated the associations of urine kidney tubule biomarkers with estimated glomerular filtration rate (eGFR) change among middle-aged adults, when chronic diseases typically emerge.Study designAn observational cohort study.Setting & participantsA total of 1,145 participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study without CKD, hypertension, or cardiovascular disease at the year 20 visit.ExposuresSeven different biomarkers of tubular health: urine epidermal growth factor (EGF), alpha-1-microglobulin (α1m), interleukin-18, kidney injury molecule-1, monocyte chemoattractant protein-1, uromodulin, and chitinase-3-like protein 1.OutcomesTen-year eGFR change and incident reduced eGFR (new onset of eGFR < 60 mL/min/1.73 m2).Analytical approachWe examined associations of tubular health biomarkers with 10-year eGFR change and incident reduced eGFR with linear mixed models and interval-censored proportional hazards regression models, respectively. Both minimally and fully adjusted models were controlled for urine creatinine levels.ResultsThe mean age of participants was 44.8 ± 3.7 years, with 39% African American and 56% female. The average 10-year change in eGFR was -18.6 mL/min/1.73 m2 (95% CI, -19.4 to -17.8). In contrast to the other tubular biomarkers, which showed conflicting results, EGF demonstrated strong, consistent associations with both kidney outcomes. Each 1-standard deviation (SD) higher EGF was associated with a 2.37 mL/min/1.73 m2 (95% CI, 0.64-4.10) smaller 10-year decrease in eGFR and a 42% (95% CI, 4%-64%) lower risk of incident reduced eGFR in the fully adjusted model.LimitationsObservational design, measurements of eGFR were done only at 5-year intervals during follow-up.ConclusionsIn middle-aged, community-dwelling adults without hypertension, cardiovascular disease or CKD, higher urine EGF concentrations are associated with slower eGFR decline, whereas other kidney tubule biomarkers lacked a consistent association with kidney function decline.

Dataset Information

Epidermal Growth Factor Pathway in the Age-Related Decline of Oligodendrocyte Regeneration.

Publications

Epidermal Growth Factor Pathway in the Age-Related Decline of Oligodendrocyte Regeneration.

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