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Neuroendocrine drivers of risk and resilience: The influence of metabolism & mitochondria.

ABSTRACT: The manifestation of risk versus resilience has been considered from varying perspectives including genetics, epigenetics, early life experiences, and type and intensity of the challenge with which the organism is faced. Although all of these factors are central to determining risk and resilience, the current review focuses on what may be a final common pathway: metabolism. When an organism is faced with a perturbation to the environment, whether internal or external, appropriate energy allocation is essential to resolving the divergence from equilibrium. This review examines the potential role of metabolism in the manifestation of stress-induced neural compromise. In addition, this review details the current state of knowledge on neuroendocrine factors which are poised to set the tone of the metabolic response to a systemic challenge. The goal is to provide an essential framework for understanding stress in a metabolic context and appreciation for key neuroendocrine signals.

SUBMITTER: Turkson S

PROVIDER: S-EPMC6886586 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Neuroendocrine drivers of risk and resilience: The influence of metabolism & mitochondria.

Turkson Susie S Kloster Alix A Hamilton Peter J PJ Neigh Gretchen N GN

Frontiers in neuroendocrinology 20190706

The manifestation of risk versus resilience has been considered from varying perspectives including genetics, epigenetics, early life experiences, and type and intensity of the challenge with which the organism is faced. Although all of these factors are central to determining risk and resilience, the current review focuses on what may be a final common pathway: metabolism. When an organism is faced with a perturbation to the environment, whether internal or external, appropriate energy allocati ...[more]

PMID: 31288042

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Project description:IntroductionIdentification of high-risk people for Alzheimer's disease (AD) is critical for prognosis and early management. Longitudinal epidemiologic studies have observed heterogeneity in the brain and cognitive aging. Brain resilience was described as above-expected cognitive function. The "resilience" framework has been shown to correlate with individual characteristics such as genetic factors and age. Besides, accumulative evidence has confirmed the association of mitochondria with the pathogenesis of AD. However, it is challenging to assess resilience through genetic metrics, in particular incorporating mitochondria-associated loci.ObjectivesIn this paper, we first demonstrated that polygenic risk scores (PRS) could characterize individuals' resilience levels. Then, we indicated that mitochondria-associated loci could improve the performance of PRSs, providing more reliable measurements for the prevention and diagnosis of AD.MethodsThe discovery (N = 1,550) and independent validation samples (N = 2,090) were used to construct nine types of PRSs containing mitochondria-related loci (PRSMT) from both biological and statistical aspects and combined them with known AD risk loci derived from genome-wide association studies (GWAS).Individuals' levels of brain resilience were comprehensively measured by linear regression models using eight pathological characteristics.ResultsIt was found that PRSs could characterize brain resilience levels (e.g., Pearson correlation test Pmin = 7.96×10-9). Moreover, the performance of PRS models could be efficiently improved by incorporating a small number of mitochondria-related loci (e.g., Pearson correlation test P improved from 1.41×10-3 to 6.09×10-6). PRSs' ability to characterize brain resilience was validated. More importantly, by incorporating some mitochondria-related loci, the performance of PRSs in measuring brain resilience could be significantly improved.ConclusionOur findings imply that mitochondria may play an important role in brain resilience, and targeting mitochondria may open a new door to AD prevention and therapy.

Dataset Information

Neuroendocrine drivers of risk and resilience: The influence of metabolism & mitochondria.

Publications

Neuroendocrine drivers of risk and resilience: The influence of metabolism & mitochondria.

Similar Datasets

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