Role of Neuroglobin in the Neuroprotective Actions of Estradiol and Estrogenic Compounds

Abstract

Estradiol exerts neuroprotective actions that are mediated by the regulation of a variety of signaling pathways and homeostatic molecules. Among these is neuroglobin, which is upregulated by estradiol and translocated to the mitochondria to sustain neuronal and glial cell adaptation to injury. In this paper, we will discuss the role of neuroglobin in the neuroprotective mechanisms elicited by estradiol acting on neurons, astrocytes and microglia. We will also consider the role of neuroglobin in the neuroprotective actions of clinically relevant synthetic steroids, such as tibolone. Finally, the possible contribution of the estrogenic regulation of neuroglobin to the generation of sex differences in brain pathology and the potential application of neuroglobin as therapy against neurological diseases will be examined.

The modulation of potassium channels by estrogens facilitates neuroprotection

“…17β-Estradiol (E2), an isomer of estradiol that is the most potent estrogen, is able to induce upregulation of the expression of neuroprotectant neuroglobin (NGB) to counteract H 2 O 2induced apoptosis (De Marinis et al, 2013;Barreto et al, 2021). Exposure to 17β-estradiol also protects the brain against reperfusion injury after acute ischemic insults by reducing lesion formation and brain atrophy, as well as improving cerebral blood flow in rat ischemic stroke (Carpenter et al, 2016).…”

“…Modulation of the hippocampal function by estrogens contributes to the estrogenic facilitation of learning and memory through diverse aspects, such as intracellular cascade, dendritic spinogenesis, and synaptic function and plasticity, and it protects hippocampal cells against excitotoxicity arising from drugs ( Taxier et al, 2020 ). 17β-Estradiol (E2), an isomer of estradiol that is the most potent estrogen, is able to induce upregulation of the expression of neuroprotectant neuroglobin (NGB) to counteract H 2 O 2 -induced apoptosis ( De Marinis et al, 2013 ; Barreto et al, 2021 ). Exposure to 17β-estradiol also protects the brain against reperfusion injury after acute ischemic insults by reducing lesion formation and brain atrophy, as well as improving cerebral blood flow in rat ischemic stroke ( Carpenter et al, 2016 ).…”

Respirasome Proteins Are Regulated by Sex-Hormone Interactions in the Brain

“…Interestingly, menopause also increases the risk of Parkinson’s disease in women [ 4 ], even though there are 50% more males with Parkinson’s than females. Given the neurodegenerative nature of these diseases, it is believed that this relationship may be associated with the neuroprotective effects of oestrogens [ 5 , 6 , 7 ]. However, little is known about reprogrammed responses to hormone replacement therapies following hormonal deprivation, and if such reprogramming is preventable or rescuable.…”

Biological Implications of a Stroke Therapy Based in Neuroglobin Hyaluronate Nanoparticles. Neuroprotective Role and Molecular Bases

“…Accumulating evidence has clearly demonstrated that the oxygen-binding protein Ngb [ 12 ] is an endogenous neuroprotective molecule in numerous neurological diseases, and particularly against hypoxic/ischemic (H/I) and oxidative stress-related insults [ 13 ]. Its neuroprotective activity has been described in numerous publications from cultured neurons to animal models [ 14 , 15 , 16 , 17 , 18 , 19 ], although the molecular mechanisms on which Ngb bases its neuroprotective ability are just beginning to be investigated [ 20 ]. Specifically, it is known that Ngb interacts with proteins involved in signal transduction and regulation, such as PI3K or AMP-activated protein kinase (AMPK), both involved in mitochondrial functions and cell metabolism [ 21 ].…”