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Published on: June 13, 2021
NURR1 Alterations in Perinatal Stress: A First Step towards Late-Onset Diseases? A Narrative Review
Laura Bordoni1, Irene Petracci2, Jean Calleja-Agius3
1Unit of Molecular Biology and Nutrigenomics, School of Pharmacy, University of Camerino, 62032 Camerino, Italy.
Insights
Perinatal stress can alter Nuclear Receptor Related 1 protein (NURR1) gene expression, potentially leading to long-term health issues in offspring. NURR1 may serve as a biomarker and therapeutic target for these late-onset diseases.
Area of Science:
- Neuroscience
- Developmental Biology
- Epigenetics
Background:
- Perinatal stimuli can impact long-term health programming in offspring.
- Nuclear Receptor Related 1 protein (NURR1) is crucial for dopaminergic neuron development and stress response.
- Maternal factors like obesity and infections can disrupt NURR1 expression during pregnancy.
Purpose of the Study:
- To review the role of perinatal stress in Nuclear Receptor Related 1 protein (NURR1) gene deregulation.
- To explore NURR1's potential as a mediator of late-onset health consequences from early life events.
- To discuss NURR1 as a prognostic tool and therapeutic target.
Main Methods:
- This study is a narrative review of existing literature.
- It synthesizes findings on perinatal stress, NURR1 expression, and epigenetic modifications.
- The review examines the link between early life events and adult-onset diseases via NURR1.
Main Results:
- Perinatal stress, including inflammation and neurotoxin exposure, alters NURR1 expression and epigenetic regulation.
- Such alterations in offspring may have intergenerational effects.
- NURR1 deregulation is associated with an increased risk of late-onset diseases.
Conclusions:
- Perinatal stress-induced NURR1 gene deregulation is a proposed mediator of long-term health issues.
- NURR1 holds promise as a biomarker for predicting disease risk.
- Targeting NURR1 may offer therapeutic strategies for conditions linked to early life stress.
Abstract:
Perinatal life represents a delicate phase of development where stimuli of all sorts, coming to or from the mother, can influence the programming of the future baby's health. These stimuli may have consequences that persist throughout adulthood. Nuclear receptor related 1 protein (NURR1), a transcription factor with a critical role in the development of the dopaminergic neurons in the midbrain, mediates the response to stressful environmental stimuli in the perinatal period. During pregnancy, low-grade inflammation triggered by maternal obesity, hyperinsulinemia or vaginal infections alters NURR1 expression in human gestational tissues. A similar scenario is triggered by exposure to neurotoxic compounds, which are associated with NURR1 epigenetic deregulation in the offspring, with potential intergenerational effects. Since these alterations have been associated with an increased risk of developing late-onset diseases in children, NURR1, alone, or in combination with other molecular markers, has been proposed as a new prognostic tool and a potential therapeutic target for several pathological conditions. This narrative review describes perinatal stress associated with NURR1 gene deregulation, which is proposed here as a mediator of late-onset consequences of early life events.
