Modulators of Endogenous Neuroprotection: Estrogen, Corticotropin-releasing Hormone and Endocannabinoids

Summary

Age-associated neurodegenerative disorders are among the most challenging problems of our aging society. Alzheimer’s disease is affecting people with increasing frequency, since there is a clear relationship between the incidence of this detrimental disorder and age. Other neurodegenerative disorders, including Parkinson’s disease, stroke and amyotrophic lateral sclerosis, are also frequently observed in our aging society. For most of these diseases, no causal therapy has yet been identified. Many of the treatments given to patients that are affected by these disorders have different side effects, and therefore the search is on to identify novel molecular approaches that may lead to a more effective therapy. In addition to treatment after the onset of these disorders, preventive strategies are of great importance. The brain itself may lead us to such novel preventive avenues, since large areas of the brain and the central nervous system in general resist detrimental processes and remain functional, even in late stages of the disorders mentioned. Such intrinsic neuroprotective and neuropreventive signals may indeed help to stabilize brain function and to make the central nervous system more resistant to the development of neurodegenerative disorders. Among these signals, we identified a potent neuroprotective role for the female sex hormone, estrogen, the corticotropin-releasing hormone (CRH) and endogenously produced and secreted cannabinoids (endocannabinoids). These hormones are powerful neuroprotective compounds when applied in paradigms of oxidative nerve cell death. Oxidative stress is a major hallmark of many neurodegenerative processes and of aging in general. The identification of common downstream pathways induced by these hormones may be the basis for the development of novel molecular strategies for neuroprevention.