Year-end Sale % OFF 
Abstract
The progesterone derivative allopregnanolone (ALLO) is one of the most widely studied compounds among neurosteroids. Through interactions with GABA-A receptors expressed by neurons and glial cells, ALLO has been shown to affect diverse aspects of neural cell physiology, including cell proliferation and survival, migration, and gene expression. Recent data point to important roles for ALLO in different neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis (MS). Dysregulation in ALLO biosynthesis pathways has been reported in brain tissue from MS patients as well as in the central nervous system (CNS) tissue derived from MS animal models. Administration of ALLO has been shown to ameliorate neurobehavioral deficits together with neuropathology and inflammation in the CNS of animals with autoimmune demyelination. These findings are in line with previous reports indicating growth- and differentiation-promoting actions of ALLO on neurons and glial cells as well as its neuroprotective effects in the context of other CNS diseases. Nonetheless, these findings have also raised the possibility that ALLO might influence leukocyte biology and associated neuroinflammatory mechanisms independent of its neuroregenerative properties. Herein, we review the current knowledge regarding the role of ALLO in the pathogenesis of MS, and discuss the potential cellular and molecular pathways that might be influenced by ALLO in the context of disease.
Highlights
Steroids synthesized from precursors in central or peripheral nervous systems have attracted substantial attention in recent years (Mellon and Griffin, 2002; Brinton, 2013)
While the blood-brain barrier (BBB) is permissive to steroids produced by gonads and adrenals, the precise neuroanatomical segregation of the locallysynthesized steroids, i.e., neurosteroids, gives them a distinct advantage over peripheral steroids in terms of exerting regionspecific effects in the nervous system
In addition to binding to intracellular steroid receptors, some neurosteroids interact with neurotransmitter receptors, influencing the biology of select types of neural cells (Belelli and Lambert, 2005)
Summary
Administration of ALLO has been shown to ameliorate neurobehavioral deficits together with neuropathology and inflammation in the CNS of animals with autoimmune demyelination. These findings are in line with previous reports indicating growth- and differentiation-promoting actions of ALLO on neurons and glial cells as well as its neuroprotective effects in the context of other CNS diseases. These findings have raised the possibility that ALLO might influence leukocyte biology and associated neuroinflammatory mechanisms independent of its neuroregenerative properties.
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
