Title: Discovery of Neurogenic, Alzheimers Disease Therapeutics
Volume: 3
Issue: 1
Author(s): Judith Kelleher-Andersson
Affiliation:
Keywords:
Neurodegeneration, neurogenesis, Alzheimer's disease, therapeutics, signaling
Abstract: Many researchers have questioned whether new potential therapies aimed at reversing Alzheimers disease (AD) are indeed scientifically feasible. A number of approved therapies already exist for Alzheimers disease, yet these drugs only slow the disease progression for a period of time and treat the symptoms of this devastating disease. New therapies intended to reverse the disease would necessarily need to replace dead, dying and dysfunctional neurons in affected regions of the brain. This complex drug discovery problem is further complicated by the knowledge that AD is mainly an aging disorder and that aging, though not considered a disease, causes biological changes that may also need to be overcome [1]. The requirement for new, functional neurons under neurodegenerative diseases, as seen in AD and stroke suggests that an inhibitor of neuronal death, like Memantine, is insufficient to reverse the cognitive and physical loss. New neurons, or neurogenesis, may be required for real improvement or reversal of the cognitive deficit. Adult neurogenesis, first described by Altman in the early 1960s [2, 3], has more recently been observed as a response to injury or disease. Of interest was the finding that new neurons appear to migrate to disease/injury-affected areas in the brain not normally neurogenic in the adult. This pathological-stimulation of neurogenesis does not appear sufficient to stave off the disease and subsequent behavioral decline. Therefore, the desire to amplify and improve upon the neurogenesis-response to neurodegenerative disease appears warranted, if not yet feasible. The key to doing so lies in identifying what signals are required to promote neurogenesis and neuron survival, either in injury and disease or under environmental stimuli. This could provide clues for how to pharmacologically induce neurogenesis under neurodegenerative conditions. Currently, progress in identifying therapeutics that appear to promote ameliorative neurogenesis for AD is lagging behind the pharmacological induction of neurogenesis as a therapy for depression.
