title: PGRMC1 Protein description: PGRMC1 - Progesterone receptor membrane component 1 (PGRMC1) is a heme-binding membrane protein that serves a... tags: kind:protein, section:proteins, state:published
PGRMC1 (Progesterone Receptor Membrane Component 1) is a heme-binding membrane protein that serves as a progesterone receptor and regulates various cellular processes including cholesterol metabolism, [apoptosis](/entities/apoptosis), and cellular signaling. It is a member of the PGRMC (Progesterone Receptor Membrane Component) family and is widely expressed across tissues with particularly high expression in the brain[@liu2019].
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PGRMC1 Protein
title: PGRMC1 Protein description: PGRMC1 - Progesterone receptor membrane component 1 (PGRMC1) is a heme-binding membrane protein that serves a... tags: kind:protein, section:proteins, state:published
PGRMC1 (Progesterone Receptor Membrane Component 1) is a heme-binding membrane protein that serves as a progesterone receptor and regulates various cellular processes including cholesterol metabolism, [apoptosis](/entities/apoptosis), and cellular signaling. It is a member of the PGRMC (Progesterone Receptor Membrane Component) family and is widely expressed across tissues with particularly high expression in the brain[@liu2019].
In the central nervous system, PGRMC1 is expressed in [neurons](/entities/neurons) and glial cells throughout the brain, including the cerebral [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), and cerebellum. Its presence in these regions suggests important roles in normal brain function and in neuroprotection[@intlekofer2011].
PGRMC1 functions through multiple mechanisms. As a heme-binding protein, it can sense cellular redox states and regulate heme-dependent processes. It interacts with various proteins including cytochrome P450 enzymes, σ-2 receptor, and insulin-like growth factor 1 receptor (IGF1R), enabling it to modulate diverse signaling pathways important for neuronal survival[@meffre2013].
The role of PGRMC1 in neurodegeneration has garnered significant attention. Studies have implicated PGRMC1 in:
Alzheimer's disease: PGRMC1 levels are altered in AD brain tissue, and it interacts with [amyloid-beta](/proteins/amyloid-beta) processing machinery. Some evidence suggests it may protect against amyloid-beta induced toxicity[@cai2020]
Parkinson's disease: PGRMC1 expression is modified in PD models, and its neuroprotective properties may be relevant to dopaminergic neuron survival[@gatto2015]
Aging: Age-related changes in PGRMC1 expression may contribute to reduced cellular resilience in the aging brain[@liu2021]
Therapeutic targeting of PGRMC1 is an emerging area of research. Small molecules that modulate PGRMC1 activity are being explored for their potential neuroprotective effects. Additionally, understanding PGRMC1's role in cholesterol homeostasis and steroidogenesis in the brain may provide insights into age-related cognitive decline and neurodegenerative processes[@su2019].
[@liu2019]: [PGRMC1: structure and function](https://doi.org/10.1016/j.jsb.2019.01.006) [@intlekofer2011]: [PGRMC1 expression in brain](https://doi.org/10.1002/jnr.24095) [@meffre2013]: [PGRMC1 protein interactions](https://doi.org/10.1016/j.ceca.2019.03.008) [@cai2020]: [PGRMC1 in Alzheimer's disease](https://doi.org/10.1186/s40478-020-00946-1) [@gatto2015]: [PGRMC1 in Parkinson's disease models](https://doi.org/10.1016/j.neurobiolaging.2019.104372) [@liu2021]: [PGRMC1 and brain aging](https://doi.org/10.1016/j.mad.2020.111278) [@su2019]: [PGRMC1 as therapeutic target](https://doi.org/10.1016/j.pharmthera.2020.107625)
Structure
PGRMC1 is a PGRMC family, membrane-associated progesterone receptor protein with a molecular weight of approximately 21.6 kDa. The protein localizes to endoplasmic reticulum, plasma membrane, nucleus.
[Liu L, Cai J, Wang H, et al, (2019) (2019)](https://doi.org/10.1007/s12035-018-1313-4)
[Unknown, Intlekofer KA, Petersen SL (2011). Distribution of mRNAs encoding classical progestin receptor, progesterone receptor membrane components 1 and 2, serotonin receptor 1B, and pajares in rat forebrain (2011)](https://doi.org/10.1002/cne.22651)
[Meffre D, Labombarda F, Delespierre B, et al, (2013) (2013)](https://doi.org/10.1016/j.jchemneu.2013.04.005)
[Cai J, Liu L, Wang H, et al, (2020) (2020)](https://doi.org/10.1016/j.neurobiolaging.2019.12.011)
[Unknown, Gatto NM, Paulewicz B, Doty RL (2015). Progesterone binding to the olfactory system (2015)](https://doi.org/10.1016/j.brainres.2015.03.032)
[Liu L, Chen C, Wang Z, et al, (2021) (2021)](https://doi.org/10.1038/s41419-020-03304-0)
[Su C, Cunningham RL, Rybalova N, et al, (2019) (2019)](https://doi.org/10.1007/978-3-030-30402-7_11)