Multiple Aspects of Inappropriate Action of Renin–Angiotensin, Vasopressin, and Oxytocin Systems in Neuropsychiatric and Neurodegenerative Diseases

Szczepañska‐Sadowska, Ewa; Wsol, Agnieszka; Cudnoch‐Jędrzejewska, Agnieszka; Czarzasta, Katarzyna; Żera, Tymoteusz

doi:10.3390/jcm11040908

Cited by 19 publications

(12 citation statements)

References 331 publications

(508 reference statements)

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“…Increased neuronal endocytosis in sporadic AD is a potential mechanism to promote Aβ generation and neuropathology ( Cataldo et al, 1997 ; Zhou et al, 2021 ). The function of oxytocin is altered in patients with depression, AD, Parkinson’s disease, autism, and schizophrenia ( Szczepanska-Sadowska et al, 2022 ). Increasing evidence has confirmed oxytocin’s effects on energy expenditure or metabolism ( Kerem and Lawson, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Potential biomarkers of Alzheimer’s disease and cerebral small vessel disease

Zou

Huang

Zhang

et al. 2022

Front. Mol. Neurosci.

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BackgroundCerebral small vessel disease (CSVD) is associated with the pathogenesis of Alzheimer’s disease (AD). Effective treatments to alleviate AD are still not currently available. Hence, we explored markers and underlying molecular mechanisms associated with AD by utilizing gene expression profiles of AD and CSVD patients from public databases, providing more options for early diagnosis and its treatment.MethodsGene expression profiles were collected from GSE63060 (for AD) and GSE162790 (for CSVD). Differential analysis was performed between AD and mild cognitive impairment (MCI) or CSVD progression and CSVD no-progression. In both datasets, differentially expressed genes (DEGs) with the same expression direction were identified as common DEGs. Then protein-protein interaction (PPI) network was constructed for common DEGs. Differential immune cells and checkpoints were calculated between AD and MCI.ResultsA total of 146 common DEGs were identified. Common DEGs were mainly enriched in endocytosis and oxytocin signaling pathways. Interestingly, endocytosis and metabolic pathways were shown both from MCI to AD and from CSVD no-progression to CSVD progression. Moreover, SIRT1 was identified as a key gene by ranking degree of connectivity in the PPI network. SIRT1 was associated with obesity-related genes and metabolic disorders. Additionally, SIRT1 showed correlations with CD8 T cells, NK CD56 bright cells, and checkpoints in AD.ConclusionThe study revealed that the progression of AD is associated with abnormalities in gene expression and metabolism and that the SIRT1 gene may serve as a promising therapeutic target for the treatment of AD.

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Section: Discussionmentioning

confidence: 99%

Potential biomarkers of Alzheimer’s disease and cerebral small vessel disease

Zou

Huang

Zhang

et al. 2022

Front. Mol. Neurosci.

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“…They are activated by different maturation products of angiotensinogen peptides, namely angiotensin II and III. Only the AT 2 receptor is implicated in different neurological disorders such as ASD, schizophrenia, Parkinson's disease (PD) and Alzheimer's disease (Firouzabadi et al, 2016;Szczepanska-Sadowska et al, 2022). Its functions in the brain remain elusive.…”

Section: Angiotensin At 2 Receptormentioning

confidence: 99%

Towards the convergent therapeutic potential of GPCRs in autism spectrum disorders

Annamneedi

Gora

Dudas

et al. 2023

Preprint

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Autism spectrum disorders (ASD) are diagnosed in 1/100 childbirth worldwide, based on two core symptoms, deficits in social interaction and communication and stereotyped behaviours. G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors that mediate the transfer of extracellular signals to convergent intracellular signalling and downstream cellular responses that are dysregulated in ASD. Despite hundreds of GPCRs are expressed in the brain, only 23 GPCRs are genetically associated to ASD according to the Simons Foundation Autism Research Initiative (SFARI) gene database: oxytocin OTR, vasopressin V1A, V1B, metabotropic glutamate mGlu5, mGlu7, GABAB, dopamine D1, D2, D3, serotoninergic 5-HT1B, β2-adrenoceptor, cholinergic M3, adenosine A2A, A3, angiotensin AT2, cannabinoid CB1, chemokine CX3CR1, orphan GPR37, GPR85 and olfactory OR1C1, OR2M4, OR2T10, OR52M1. Here, we review the therapeutical potential of these 23 GPCRs, in addition to 5-HT2A, 5-HT6 and 5-HT7 for their relevance to ASD. We discuss their genetic association with ASD, the effects of their genetic and pharmacological manipulation in animal models and humans, their existing pharmacopeia towards core symptoms of ASD and rank them based on these evidences. Among these 23 GPCRs, we highlight that OTR, V1A, mGlu5, D2, 5-HT2A, CB1, and GPR37 are the best therapeutic targets. We conclude that the dysregulation of GPCRs and their signalling is a convergent pathological mechanism of ASD and their therapeutic potential has only begun as multiple GPCRs could mitigate ASD.

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“…Such dysregulation causes blood pressure fluctuations, impairs cerebrovascular autoregulation, increases pro-inflammatory cytokine production in the parenchyma, and induces hyperglycemia [67,[69][70][71][72]. The state of sympathetic predominance after stroke can cause catecholamines release, which activates the magnocellular neurons in PVN and SON, resulting in AVP release [73,74]. Moreover, the state of hyperglycemia following stroke (as a result of direct post-stroke hyperglycemia or exacerbation of pre-existing diabetes) may increase the number of AVP-expressing neurons in PVN and SON, resulting in increased release of AVP during stroke [75,76].…”

Section: Arginine Vasopressin Hypersecretion and Release Mechanisms D...mentioning

confidence: 99%

The Role of Arginine-Vasopressin in Stroke and the Potential Use of Arginine-Vasopressin Type 1 Receptor Antagonists in Stroke Therapy: A Narrative Review

Chojnowski

Opiełka

Gozdalski

et al. 2023

IJMS

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Stroke is a life-threatening condition in which accurate diagnoses and timely treatment are critical for successful neurological recovery. The current acute treatment strategies, particularly non-invasive interventions, are limited, thus urging the need for novel therapeutical targets. Arginine vasopressin (AVP) receptor antagonists are emerging as potential targets to treat edema formation and subsequent elevation in intracranial pressure, both significant causes of mortality in acute stroke. Here, we summarize the current knowledge on the mechanisms leading to AVP hyperexcretion in acute stroke and the subsequent secondary neuropathological responses. Furthermore, we discuss the work supporting the predictive value of measuring copeptin, a surrogate marker of AVP in stroke patients, followed by a review of the experimental evidence suggesting AVP receptor antagonists in stroke therapy. As we highlight throughout the narrative, critical gaps in the literature exist and indicate the need for further research to understand better AVP mechanisms in stroke. Likewise, there are advantages and limitations in using copeptin as a prognostic tool, and the translation of findings from experimental animal models to clinical settings has its challenges. Still, monitoring AVP levels and using AVP receptor antagonists as an add-on therapeutic intervention are potential promises in clinical applications to alleviate stroke neurological consequences.

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Multiple Aspects of Inappropriate Action of Renin–Angiotensin, Vasopressin, and Oxytocin Systems in Neuropsychiatric and Neurodegenerative Diseases

Cited by 19 publications

References 331 publications

Potential biomarkers of Alzheimer’s disease and cerebral small vessel disease

Potential biomarkers of Alzheimer’s disease and cerebral small vessel disease

Towards the convergent therapeutic potential of GPCRs in autism spectrum disorders

The Role of Arginine-Vasopressin in Stroke and the Potential Use of Arginine-Vasopressin Type 1 Receptor Antagonists in Stroke Therapy: A Narrative Review

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