Progestogen-Mediated Neuroprotection in Central Nervous System Disorders

Author(s)

Bassani, Taysa Bervian ; Bartolomeo, Cynthia Silva ; Oliveira, Rafaela Brito ; Ureshino, Rodrigo Portes

• Document type: Journal article
• Source: Neuroendocrinology; v. 113, n. 1, p. 22-pg., 2023-01-01.

Abstract

Neuroactive steroids can be synthetic or endogenous molecules produced by neuronal and glial cells and peripheral glands. Examples include estrogens, testosterone, progesterone and its reduced metabolites such as 5 alpha-dihydro-progesterone and allopregnanolone. Steroids produced by neurons and glia target the nervous system and are called neurosteroids. Progesterone and analog molecules, known as progestogens, have been shown to exhibit neurotrophic, neuroprotective, antioxidant, anti-inflammatory, glial modulatory, promyelinating, and remyelinating effects in several experimental models of neurodegenerative and injury conditions. Pleiotropic mechanisms of progestogens may act synergistically to prevent neuron degeneration, astrocyte and microglial reactivity, reducing morbidity and mortality. The aim of this review is to summarize the significant findings related to the actions of progesterone and other progestogens in experimental models and epidemiological and clinical trials of some of the most prevalent and debilitating chronic neurodegenerative disorders, namely, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. We evaluated progestogen alterations under pathological conditions, how pathology modifies their levels, as well as the intracellular mechanisms and glial interactions underlying their neuroprotective effects. Furthermore, an analysis of the potential of natural progestogens and synthetic progestins as neuroprotective and regenerative agents, when administered as hormone replacement therapy in menopause, is also discussed. (AU)

• FAPESP's process: 20/04709-8 - Evaluation of potential therapeutically compounds for SARS-CoV-2: focus on estrogen-related compounds, autophagy modulators and ACE2
• Grantee: Rodrigo Portes Ureshino
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/20796-2 - Study of estrogen receptors mediated autophagy against tau toxicity in cell and zebrafish models
• Grantee: Rodrigo Portes Ureshino
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 18/02762-9 - Evaluation of estrogen-mediated neuroprotection in cellular model of the tauopathy
• Grantee: Rafaela Brito Oliveira
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 17/23616-8 - Analysis of progestagen receptors-mediated autophagy against tau toxicity in cell model of tauopathy
• Grantee: Taysa Bervian Bassani
• Support Opportunities: Scholarships in Brazil - Post-Doctoral