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Don't forget astrocytes when targeting Alzheimer's disease.

ABSTRACT: Astrocytes are essential for CNS health, regulating homeostasis, metabolism, and synaptic transmission. In addition to these and many other physiological roles, the pathological impact of astrocytes ("reactive astrocytes") in acute trauma and chronic disease like Alzheimer's disease (AD) is well established. Growing evidence supports a fundamental and active role of astrocytes in multiple neurodegenerative diseases. With a growing interest in normal astrocyte biology, and countless studies on changes in astrocyte function in the context of disease, it may be a surprise that no therapies exist incorporating astrocytes as key targets. Here, we examine unintentional effects of current AD therapies on astrocyte function and theorize how astrocytes may be intentionally targeted for more efficacious therapeutic outcomes. Given their integral role in normal neuronal functioning, incorporating astrocytes as key criteria for AD drug development can only lead to more effective therapies for the millions of AD sufferers worldwide. LINKED ARTICLES: This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc.

SUBMITTER: Sadick JS

PROVIDER: S-EPMC6715613 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Don't forget astrocytes when targeting Alzheimer's disease.

Sadick Jessica S JS Liddelow Shane A SA

British journal of pharmacology 20190219 18

Astrocytes are essential for CNS health, regulating homeostasis, metabolism, and synaptic transmission. In addition to these and many other physiological roles, the pathological impact of astrocytes ("reactive astrocytes") in acute trauma and chronic disease like Alzheimer's disease (AD) is well established. Growing evidence supports a fundamental and active role of astrocytes in multiple neurodegenerative diseases. With a growing interest in normal astrocyte biology, and countless studies on ch ...[more]

PMID: 30636042

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Project description:Metabolic bone disease of prematurity (MBD) is a condition of reduced bone mineral content (BMC) compared to that expected for gestational age (GA). Preterm birth interrupts the physiological process of calcium (Ca) and phosphorus (P) deposition that occurs mostly in the third trimester of pregnancy, leading to an inadequate bone mineralization during intrauterine life (IUL). After birth, an insufficient intake of Ca and P carries on this alteration, resulting in overt disease. If MBD is often a self-limited condition, in some cases it could hesitate the permanent alteration of bone structures with growth faltering and failure to wean off mechanical ventilation due to excessive chest wall compliance. Despite advances in neonatal intensive care, MBD is still frequent in preterm infants, with an incidence of 16−23% in very-low-birth-weight (VLBW, birth weight <1500 g) and 40−60% in extremely low-birth-weight (ELBW, birth weight <1000 g) infants. Several risk factors are associated with MBD (e.g., malabsorption syndrome, parenteral nutrition (PN), pulmonary bronchodysplasia (BPD), necrotizing enterocolitis (NEC), and some chronic medications). The aim of this study was to evaluate the rate of MBD in a cohort of VLBWI and the role of some risk factors. We enrolled 238 VLBWIs (107 male). 52 subjects were classified as increased risk (G1) and 186 as standard risk (G2) according to serum alkaline phosphatase (ALP) and phosphorus (P) levels. G1 subjects have lower GA (p < 0.01) and BW (p < 0.001). Moreover, they need longer PN support (p < 0.05) and invasive ventilation (p < 0.01). G1 presented a higher rate of BPD (p = 0.026). At linear regression analysis, BW and PN resulted as independent predictor of increased risk (p = 0.001, p = 0.040, respectively). Preventive strategies are fundamental to prevent chronic alteration in bone structures and to reduce the risk of short stature. Screening for MBD based on serum ALP could be helpful in clinical practice to identify subjects at increased risk.

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Don't forget astrocytes when targeting Alzheimer's disease.

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Don't forget astrocytes when targeting Alzheimer's disease.

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