Decoding signaling pathways involved in prolactin-induced neuroprotection: A review

Molina-Salinas, G.; Rivero-Segura, Nadia Alejandra; Cabrera-Reyes, Erika Alejandra; Rodríguez-Chávez, V.; Langley, E. Farris; Cerbón, Marco

doi:10.1016/j.yfrne.2021.100913

Cited by 17 publications

(11 citation statements)

References 179 publications

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“…PRL (prolactin) encodes the anterior pituitary hormone prolactin and is involved in the regulation of many signaling pathways, including amyloid fibril formation, prolactin signaling, growth hormone receptor signaling, cytokine signaling in the immune system, and protein metabolism pathways ( Bole-Feysot et al, 1998 ; Jacob et al, 2016 ). Prolactin, a pleiotropic hormone, has many functions in the brain, such as maternal behavior, neurogenesis, and neuronal plasticity, among others ( Molina-Salinas et al, 2021 ). Recently, it has been reported to have a significant role in neuroprotection against excitotoxicity ( Molina-Salinas et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

Sleep and Late-Onset Alzheimer’s Disease: Shared Genetic Risk Factors, Drug Targets, Molecular Mechanisms, and Causal Effects

et al. 2022

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Late-onset Alzheimer’s disease (AD) is associated with sleep-related phenotypes (SRPs). The fact that whether they share a common genetic etiology remains largely unknown. We explored the shared genetics and causality between AD and SRPs by using high-definition likelihood (HDL), cross-phenotype association study (CPASSOC), transcriptome-wide association study (TWAS), and bidirectional Mendelian randomization (MR) in summary-level data for AD (N = 455,258) and summary-level data for seven SRPs (sample size ranges from 359,916 to 1,331,010). AD shared a strong genetic basis with insomnia (rg = 0.20; p = 9.70 × 10–5), snoring (rg = 0.13; p = 2.45 × 10–3), and sleep duration (rg = −0.11; p = 1.18 × 10–3). The CPASSOC identifies 31 independent loci shared between AD and SRPs, including four novel shared loci. Functional analysis and the TWAS showed shared genes were enriched in liver, brain, breast, and heart tissues and highlighted the regulatory roles of immunological disorders, very-low-density lipoprotein particle clearance, triglyceride-rich lipoprotein particle clearance, chylomicron remnant clearance, and positive regulation of T-cell–mediated cytotoxicity pathways. Protein–protein interaction analysis identified three potential drug target genes (APOE, MARK4, and HLA-DRA) that interacted with known FDA-approved drug target genes. The CPASSOC and TWAS demonstrated three regions 11p11.2, 6p22.3, and 16p11.2 may account for the shared basis between AD and sleep duration or snoring. MR showed insomnia had a causal effect on AD (ORIVW = 1.02, PIVW = 6.7 × 10–6), and multivariate MR suggested a potential role of sleep duration and major depression in this association. Our findings provide strong evidence of shared genetics and causation between AD and sleep abnormalities and advance our understanding of the genetic overlap between them. Identifying shared drug targets and molecular pathways can be beneficial for treating AD and sleep disorders more efficiently.

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Section: Resultsmentioning

confidence: 99%

Sleep and Late-Onset Alzheimer’s Disease: Shared Genetic Risk Factors, Drug Targets, Molecular Mechanisms, and Causal Effects

et al. 2022

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“…For example, PRL can in uence sleep structure, and PRL de cient mice display less rapid eye movement (REM) sleep than wild-type mice [47]. Molina-Salinas et al have shown that PRL can inhibit glutamate excitotoxicity through the AKT and STAT5 pathways, thereby protecting neuronal cells and decreasing the progression of Alzheimer's disease [22]. Evidence has suggested that somatostatin expression is down-regulated in early aging brains in snoring samples, leading to a progressive decrease in PRL and neprilysin activity and resulting in amyloid b (Ab) peptide accumulation in AD patients [48].…”

Section: Discussionmentioning

confidence: 99%

“…PRL (prolactin) encodes the anterior pituitary hormone prolactin and is involved in the regulation of many signaling pathways, including amyloid bril formation, prolactin signaling, growth hormone receptor signaling, cytokine signaling in the immune system and protein metabolism pathway [20,21]. Prolactin, a pleiotropic hormone, has many functions in the brain, such as maternal behavior, neurogenesis, and neuronal plasticity, among others [22]. Recently, it has been reported to have a signi cant role in neuroprotection against excitotoxicity [22].…”

Section: Cross Trait Meta-analysis Between Ad and Srpsmentioning

confidence: 99%

“…Prolactin, a pleiotropic hormone, has many functions in the brain, such as maternal behavior, neurogenesis, and neuronal plasticity, among others [22]. Recently, it has been reported to have a signi cant role in neuroprotection against excitotoxicity [22]. PATJ encodes a protein with multiple PDZ domains and plays a role in the cell junction organization, tight junction, hippo signaling pathway.…”

Section: Cross Trait Meta-analysis Between Ad and Srpsmentioning

confidence: 99%

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Sleep and Alzheimer’s Disease: Shared Genetic Risk Factors, Drug Targets, Molecular Mechanisms, and Causal Effects

Chen

Wang

Jia

et al. 2021

Preprint

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Background: Alzheimer’s disease (AD) was associated with sleep-related phenotypes (SRPs). Whether they share common genetic etiology remains largely unknown. We explored the shared genetics and causality between AD and SRPs by using high-definition likelihood (HDL), cross phenotype association study (CPASSOC), transcriptome wide association study (TWAS), and bidirectional Mendelian randomization (MR) in summary-level data for AD (n = 79145) and summary-level data for seven SRPs (sample size ranges from 345552 to 386577). Results: AD shared strong genetic basis with insomnia (rg = 0.20; P = 9.70×10-5), snoring (rg = 0.13; P = 2.45×10-3), and sleep duration (rg = -0.11; P = 1.18×10-3). CPASSOC identifies 31 independent loci shared between AD and SRPs, including four novel shared loci. Functional analysis and TWAS showed shared genes were enriched in liver, brain, breast, and heart tissues, and highlighted the regulatory role of immunological disorders, very-low-density lipoprotein particle clearance, triglyceride-rich lipoprotein particle clearance, chylomicron remnant clearance and positive regulation of T cell mediated cytotoxicity pathways. Protein-protein interaction analysis provided three potential drug target genes (APOE, MARK4 and HLA-DRA) that interacted with known FDA-approved drug target genes. CPASSOC and TWAS demonstrated three regions 11p11.2, 6p22.3 and 16p11.2 may account for the shared basis between AD and sleep duration or snoring. MR showed AD had causal effect on sleep duration (βIVW = -0.056, PIVW = 1.03×10-3). Conclusion: Our findings provide strong evidence of shared genetics and causation between AD and sleep, and advance our understanding the genetic overlap between them. Identifying shared drug targets and molecular pathways can be beneficial to treat AD and sleep disorders more efficiently.

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“…All these data suggest a role of PRL in the regulation of early vertebrate development. Indeed, excellent reviews on the molecular and physiological functions of PRL centered on postnatal and adult processes (e.g., lactation, reproduction, neuroprotection, and maternal behavior) have been published [2][3][4][5][6]. Thus, despite being a hormone with several physiological actions, scarce information about its role during embryonic and fetal development has been published.…”

Section: Introductionmentioning

confidence: 99%

Prolactin from Pluripotency to Central Nervous System Development

Martínez-Alarcón¹,

García‐López²,

Mora³

et al. 2021

Neuroendocrinology

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Prolactin (PRL) is a versatile hormone that exerts more than 300 functions in vertebrates, mainly associated with physiological effects in adult animals. Although the process that regulates early development is poorly understood, evidence suggests a role of PRL in the early embryonic development regarding pluripotency and nervous system development. Thus, PRL could be a crucial regulator in oocyte preimplantation and maturation as well as during diapause, a reversible state of blastocyst development arrest that shares metabolic, transcriptomic, and proteomic similarities with pluripotent stem cells in the naïve state. Thus, we analyzed the role of the hormone during those processes, which involve the regulation of its receptor and several signaling cascades (Jak/Mapk, Jak/Stat, and PI3k/Akt), resulting in either a plethora of physiological actions or their dysregulation, a factor in developmental disorders. Finally, we propose models to improve the knowledge on PRL function during early development.

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Decoding signaling pathways involved in prolactin-induced neuroprotection: A review

Cited by 17 publications

References 179 publications

Sleep and Late-Onset Alzheimer’s Disease: Shared Genetic Risk Factors, Drug Targets, Molecular Mechanisms, and Causal Effects

Sleep and Late-Onset Alzheimer’s Disease: Shared Genetic Risk Factors, Drug Targets, Molecular Mechanisms, and Causal Effects

Sleep and Alzheimer’s Disease: Shared Genetic Risk Factors, Drug Targets, Molecular Mechanisms, and Causal Effects

Prolactin from Pluripotency to Central Nervous System Development

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