Progesterone receptor membrane component 1: An integrative review

Cahill, Michael A.

doi:10.1016/j.jsbmb.2007.02.002

Cited by 323 publications

(413 citation statements)

References 103 publications

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“…However, PGRMC1 is expressed in many cell types and has progesterone dependent and independent actions depending in part on its cellular location. 5 Although PGRMC1 is present at the mid-zone/mid-body of the spindle apparatus of both somatic and germ cells, the question arises as to whether PGRMC1 plays an essential role in the mechanism through which chromosomes segregate. This question was elegantly addressed in a paper from The Lodde Laboratory, which was recently published in Cell Cycle.…”

mentioning

confidence: 99%

PGRMC1 and the faithful progression through mitosis and meiosis

Luciano

Peluso

2016

Cell Cycle

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mentioning

confidence: 99%

PGRMC1 and the faithful progression through mitosis and meiosis

Luciano

Peluso

2016

Cell Cycle

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“…Thus, variation in the degree to which exogenous progesterone impacts rotifer reproduction (Snell & DesRosiers, 2008) Amino acid substitutions that accrued over time may have altered MAPR function even with purifying selection. The large number of predicted phosphorylation sites supports a role in signal transduction, as reviewed by Cahill (2007). Variation in predicted sites among rotifers could allow for differential signal transduction, though more research is required to confirm the sites' function.…”

Section: Discussionmentioning

confidence: 88%

“…In phylogenetic analyses of a diverse set of MAPR homologs, although support for nodes was generally poor different methods returned the same best tree topology with the B. manjavacas MAPR grouped deeply within the clade of metazoan MAPRs (Fig. 1b), distinct from conserved paralogs cytochrome b5 and Neudesin (Cahill, 2007).…”

Section: Resultsmentioning

confidence: 98%

“…Searches of a brachionid transcriptome yielded an expressed sequence tag (EST) contig identified as a potential membrane associated progesterone receptor (MAPR) (Snell & DesRosiers, 2008). The MAPR gene family is proposed to have originated from an ancestral cytochrome b5 (Cyt b5), and contains Neudesin and the vertebrate-specific paralogs progesterone receptor membrane component (PGRMC) 1 and 2 (Cahill, 2007). Functions of MAPR proteins vary across phyla and range from inhibition of apoptosis in ovarian granulosa cells to cholesterol synthesis and axon guidance (Cahill, 2007;Rohe et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…The MAPR gene family is proposed to have originated from an ancestral cytochrome b5 (Cyt b5), and contains Neudesin and the vertebrate-specific paralogs progesterone receptor membrane component (PGRMC) 1 and 2 (Cahill, 2007). Functions of MAPR proteins vary across phyla and range from inhibition of apoptosis in ovarian granulosa cells to cholesterol synthesis and axon guidance (Cahill, 2007;Rohe et al, 2009). While progesterone binding cannot be assumed by homology, it is notable that the Brachionus putative MAPR is the only known candidate receptor for progesterone.…”

Section: Introductionmentioning

confidence: 99%

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Molecular evolution of the membrane associated progesterone receptor in the Brachionus plicatilis (Rotifera, Monogononta) species complex

2010

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Many studies have investigated physiological roles of the membrane associated progesterone receptor (MAPR), but little is known of its evolution. Marked variations in response to exogenous progesterone have been reported for four brachionid rotifer species, suggesting differences in progesterone signaling and reception. Here we report sequence variation for the MAPR gene in the Brachionus plicatilis species complex. Phylogenetic analysis of this receptor is compared with relatedness based on cytochrome c oxidase subunit 1 sequences.Nonsynonymous to synonymous site substitution rate ratios, amino acid divergence, and variations in predicted phosphorylation sites are examined to assess evolution of the MAPR among brachionid clades.

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Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer's disease modification

Izzo

Yuede

LaBarbera

et al. 2021

Alzheimer's & Dementia

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Introduction Amyloid beta (Aβ) oligomers are one of the most toxic structural forms of the Aβ protein and are hypothesized to cause synaptotoxicity and memory failure as they build up in Alzheimer's disease (AD) patients’ brain tissue. We previously demonstrated that antagonists of the sigma‐2 receptor complex effectively block Aβ oligomer toxicity. CT1812 is an orally bioavailable, brain penetrant small molecule antagonist of the sigma‐2 receptor complex that appears safe and well tolerated in healthy elderly volunteers. We tested CT1812's effect on Aβ oligomer pathobiology in preclinical AD models and evaluated CT1812's impact on cerebrospinal fluid (CSF) protein biomarkers in mild to moderate AD patients in a clinical trial (ClinicalTrials.gov NCT02907567). Methods Experiments were performed to measure the impact of CT1812 versus vehicle on Aβ oligomer binding to synapses in vitro, to human AD patient post mortem brain tissue ex vivo, and in living APPSwe/PS1dE9 transgenic mice in vivo. Additional experiments were performed to measure the impact of CT1812 versus vehicle on Aβ oligomer‐induced deficits in membrane trafficking rate, synapse number, and protein expression in mature hippocampal/cortical neurons in vitro. The impact of CT1812 on cognitive function was measured in transgenic Thy1 huAPPSwe/Lnd+ and wild‐type littermates. A multicenter, double‐blind, placebo‐controlled parallel group trial was performed to evaluate the safety, tolerability, and impact on protein biomarker expression of CT1812 or placebo given once daily for 28 days to AD patients (Mini‐Mental State Examination 18–26). CSF protein expression was measured by liquid chromatography with tandem mass spectrometry or enzyme‐linked immunosorbent assay in samples drawn prior to dosing (Day 0) and at end of dosing (Day 28) and compared within each patient and between pooled treated versus placebo‐treated dosing groups. Results CT1812 significantly and dose‐dependently displaced Aβ oligomers bound to synaptic receptors in three independent preclinical models of AD, facilitated oligomer clearance into the CSF, increased synaptic number and protein expression in neurons, and improved cognitive performance in transgenic mice. CT1812 significantly increased CSF concentrations of Aβ oligomers in AD patient CSF, reduced concentrations of synaptic proteins and phosphorylated tau fragments, and reversed expression of many AD‐related proteins dysregulated in CSF. Discussion These preclinical studies demonstrate the novel disease‐modifying mechanism of action of CT1812 against AD and Aβ oligomers. The clinical results are consistent with preclinical data and provide evidence of target engagement and impact on fundamental disease‐related signaling pathways in AD patients, supporting further development of CT1812.

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Progesterone receptor membrane component 1: An integrative review

Cited by 323 publications

References 103 publications

PGRMC1 and the faithful progression through mitosis and meiosis

PGRMC1 and the faithful progression through mitosis and meiosis

Molecular evolution of the membrane associated progesterone receptor in the Brachionus plicatilis (Rotifera, Monogononta) species complex

Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer's disease modification

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