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Progestogen-Mediated Neuroprotection in Central Nervous System Disorders

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Autor(es):
Bassani, Taysa Bervian ; Bartolomeo, Cynthia Silva ; Oliveira, Rafaela Brito ; Ureshino, Rodrigo Portes
Número total de Autores: 4
Tipo de documento: Artigo Científico
Fonte: Neuroendocrinology; v. 113, n. 1, p. 22-pg., 2023-01-01.
Resumo

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)

Processo FAPESP: 20/04709-8 - Avaliação de compostos com potencial terapêutico para SARS-CoV-2: enfoque em compostos com atividade estrogênica, moduladores da autofagia e ECA2
Beneficiário:Rodrigo Portes Ureshino
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 16/20796-2 - Estudo da autofagia mediada pelos receptores de estrógeno para combater a toxicidade da proteína tau em modelos celular e animal de zebrafish
Beneficiário:Rodrigo Portes Ureshino
Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
Processo FAPESP: 18/02762-9 - Avaliação da neuroproteção mediada pelo estrógeno em modelo celular de tauopatia
Beneficiário:Rafaela Brito Oliveira
Modalidade de apoio: Bolsas no Brasil - Mestrado
Processo FAPESP: 17/23616-8 - Análise da autofagia mediada pelos receptores de progestágenos para combater a toxicidade da proteína tau em modelo celular de tauopatia
Beneficiário:Taysa Bervian Bassani
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado