LAUSR

The term "Neurosteroids" designates pregnenolone-derived bioactive compounds that are synthesized or catalyzedbyneural cells andact locally on the central orperipheral nervous systems.At themolecular level, the actions of neurosteroids are mainly mediated through membrane receptors i.e. via their cognate receptors and/or via allosteric modulation of other receptors. At the cellular level, neurosteroids act as neurohormones, neuromodulators, neurotransmitters and/or neurotrophic factors. At the organismal level, neurosteroids regulate several physiological processes including arousal, sleep, learning, social and sexual behaviors. Thus, neurosteroids are now considered an important class of intercellular/intracellular signalingmolecules in thenervous system, inverymuch the sameasneurotransmitters, neuropeptides and growth factors. Not surprisingly, neurosteroids appear to be implicated in a number of pathophysiological conditions such as pain, neurodegenerative diseases, autism, stress, anxiety, depression, etc. Therefore, drugs targeting neurosteroid biosynthetic enzymes or neurosteroid receptors have strong potential for the development of novel therapeutic approaches. This Research Topic compiles a series of review and original articles that provide a broad view of the current knowledge on the biosynthesis, functional roles and pathophysiological implications of neurosteroids, and highlights new concepts in this field. We want to dedicate this Research Topic to the memory of our colleague and dear friend Kazuyoshi Tsutsui, an undisputed leader in neurosteroid research who, very sadly, passed away on September 16, 2021. Progesterone and allopregnanolone are two neuroactive steroids that act primarily through membrane receptors (1). Progesterone can activate five metabotropic membrane receptors belonging to the progestin and adipoQ receptor (PAQR) family that are distinct from the GPCR family (2). Allopregnanolone and its 3b-methylated synthetic analog ganaxolone act as positive allosteric modulators of GABAA receptors (Pinna). The review by Thomas and Pang summarizes the current knowledge on the neuroprotective actions of allopregnanolone and ganaxolone. Concurrently, Pinna describes the long journey between the discovery of allopregnanolone in the adrenal cortex (3) and the characterization of its anxiolytic and antidepressant properties (4, 5). The recent validation of allopregnanolone-based treatment of postpartum depression (6) opens new avenues for the development of other neurosteroid-derived drugs in neuropsychiatry. Apolipoprotein A1 regulatory protein-1 (ARP-1), a member of the steroid receptor superfamily whose ligand is unknown (orphan receptor), regulates transcriptional activity of numerous genes