The neuroprotective actions of corticotropin releasing hormone

Corticotropin-releasing hormone (CRH) modulates the activity of the hypothalamic-pituitary-adrenal (HPA) axis, and has a key role in mediating neuroendocrine effects that occur in response to stressful stimuli. Disruption of the CRH system however has been shown to be closely associated with the progression of Alzheimer's disease (AD), and these observations prompted an investigation into the potential neuroprotective effects of the hormone. In addition to its regulatory affects on the molecular processes that underlie AD i.e., amyloid precursor protein (APP) processing and potentially tau phosphorylation, evidence is provided that the neuroprotective effects of CRH are mediated by a number of diverse mechanisms. These stem from activation of its high affinity receptor, the CRH type 1 receptor, and involve the induction of protective intracellular pathways including PKA-CREB that eventually lead to expression of neurotrophic factors. Conversely, inhibition of harmful events, such as caspase activation during apoptosis may also occur. Taken together, an impressive amount of evidence has accumulated recently, highlighting this new and potentially important function of CRH. (c) 2005 Elsevier Ireland Ltd. All rights reserved.