androgens exert direct neuroprotective effects on the brain: a review of pre-clinical evidences

Objective. To review available data describing pathways directly modulated by androgens that underlie brain neuroprotection. Material and methods. A literature search was performed in July 2010 using the commercially available Medline online engine search to retrieve studies (from 1991 to 2010) on the mechanisms mediating the role of androgens on brain neuroprotection. A combination of the following medical subject headings was used: androgens, brain, neuroprotection, androgen receptor (AR). Results. Direct androgen-dependent signaling pathways are active in both neuronal and glial compartments within the brain. Within physiological ranges , androgens promote β-amyloid and protein tau homeostasis, enhance antioxidant mechanisms, promote neuron viability and survival, control reac-tive gliosis, neuronal excitability and modulate water homeostasis. Conclusions. Androgens directly exert neuroprotective effects in the brain thus counteracting neurodegenerative diseases and improving recovery after injury. These evidences provide rationales for androgen replacement therapy in hypogonadal subjects for the prevention, the therapy or the control of progression of neurodegenerative and neurotoxic diseases.