The role of sex and sex Hormones in Neurodegenerative Diseases Downloaded from https://academic.oup.com/edrv/advance-article-abstract/doi/10.1210/endrev/bnz005/5572525 by Università degli Studi di Milano user on 24 September 2019
Elisabetta Vegeto, Alessandro Villa, Sara Della Torre, Valeria Crippa, Paola Rusmini,
Riccardo Cristofani, Mariarita Galbiati, Adriana Maggi*, Angelo Poletti*
Department of Excellence of Pharmacological and Biomolecular Sciences
and Center of Excellence on Neurodegenerative Diseases
Università degli Studi di Milano, Italy
Key terms: Sex Hormones, Alzheimer’s disease, Parkinson’s Disease, Amyotrophic Lateral Sclerosis, Spinal and Bulbar Muscular Atrophy
*These Authors equally contributed to this manuscript
Corresponding author's contact information: Angelo Poletti, PhD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Center of Excellence on Neurodegenerative Diseases. Università degli Studi di Milano, via Balzaretti 9, 20133, Milan, Italy. Ph. +390250318215; Fax +390250318204; e-mail [email protected]
Disclosure statement. The Authors have no item to disclose
Grants: National Institute of Health Grant RO1AG027713; European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 278850 (INMiND); Fondazione Cariplo, Italy (2011-0591, 2014-0686 and 2017_0747); Fondazione Telethon, Italy (n. GGP14039, GGP19218); Fondazione AriSLA, Italy (ALS_HSPB8, ALS_Granulopathy, MLOpathy, Target_RAN), Italian Ministry of Health (n. GR-2011-02347198), Agenzia Italiana del Farmaco (AIFA) (Co_ALS), Italian Ministry of University and Research (MIUR), PRIN - Progetti di ricerca di interesse nazionale (n. 2015LFPNMN and 2017F2A2C5), MIUR progetto di eccellenza, Fondo per il Finanziamento delle Attività Base di Ricerca (FFABR-MIUR), Fondazione Regionale per la RicercaAccepted Biomedica (FRRB) (Regione Lombardia, Manuscript TRANS_ALS, project nr. 2015-0023), Università degli Studi di Milano e piano di sviluppo UNIMI - linea B, European Molecular Biology Organization (EMBO) short term fellowship (n. 537 – 2015); EU Joint Programme - Neurodegenerative Disease Research (JPND) project European Union’s Horizon 2020 research and innovation programme under grant agreement No 643417 (Grant ID: 01ED1601A, CureALS).
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Abstract Downloaded from https://academic.oup.com/edrv/advance-article-abstract/doi/10.1210/endrev/bnz005/5572525 by Università degli Studi di Milano user on 24 September 2019
Neurodegenerative diseases (NDs) are a wide class of disorders of the central nervous system
(CNS) with still unknown etiology. Several factors were hypothesized to be involved in the pathogenesis of these diseases including genetic and environmental factors. Many of these diseases show a sex prevalence and sex steroids where shown to have a role in the progression of specific forms of neurodegeneration. Estrogens were reported to be neuroprotective though their action on cognate nuclear and membrane receptors, while adverse effects of male hormones have been described on neuronal cells, although some data also suggest neuroprotective activities. The response of the CNS to sex steroids is a complex and integrated process that depends on: i.) the type and amount of the cognate steroid receptor; ii.) the target cell-type, either neurons, glia or microglia. Moreover, the levels of sex steroids in the CNS fluctuate due to gonadal activities and to local metabolism and synthesis. Importantly, biochemical processes involved in the pathogenesis of NDs are increasingly being recognized different among the two sexes and to be influenced by sex steroids.
The aim of this review is to present current state-of-the-art understanding on the potential role of sex steroids and their receptors on the onset and progression of major neurodegenerative disorders, namely Alzheimer’s disease, Parkinson’s diseases, Amyotrophic Lateral Sclerosis and the peculiar motoneuronAccepted disease Spinal and Bulbar Muscular Manuscript Atrophy, in which hormonal therapy is potentially useful as disease modifier.
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Essential Points Downloaded from https://academic.oup.com/edrv/advance-article-abstract/doi/10.1210/endrev/bnz005/5572525 by Università degli Studi di Milano user on 24 September 2019