title: The Potential of Gonadal Hormone Signalling Pathways as Therapeutics for Dementia.
abstract: Dementia is an ever-expanding problem facing an ageing society. Currently, there is a sharp paucity of treatment strategies. It has long been known that sex hormones, namely 17β-estradiol and testosterone, possess neuroprotective- and cognitive-enhancing qualities. However, certain lacunae in the knowledge underlying their molecular mechanisms have delayed their use as treatment strategies in dementia. With recent advancements in pharmacology and molecular biology, especially in the development of safer selective oestrogen receptor modulators and the recent discovery of the small-molecule brain-derived neurotrophic factor receptor agonist, 7,8-dihydroxyflavone, the exploitation of these signalling pathways for clinical use has become possible. This review aims to adumbrate the evidence and hurdles underscoring the use of sex hormones in the treatment of dementia as well as discussing some direction that is required to advance the translation of evidence into practise.
authors.affiliation: Behavioural Neuroscience Laboratory, Department of Psychiatry, Monash University, Monash Medical Centre, Melbourne, VIC, 3168, Australia. xin.du@monash.edu.
authors.forename: X
authors.identifier: http://orcid.org/0000-0003-3960-5317
authors.initials: X
authors.lastname: Du
authors.affiliation: Psychoneuroendocrinology Laboratory, The Florey Institute of Neuroscience and Mental Health, Melbourne, 3052, VIC, Australia.
authors.forename: R A
authors.initials: RA
authors.lastname: Hill
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D003704:Dementia / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D042341:Gonadal Hormones / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D015398:Signal Transduction
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D042341:Gonadal Hormones
keywords: 7,8-DHF; Alzheimer’s disease; BDNF; Cognition; Dementia; Estradiol; Raloxifene; Sex hormones; Testosterone; TrkB