Neurodegenerative diseases affect nearly 220 million people worldwide, and are increasing in prevalence among many age groups. Long-term treatment options are limited in success, and are often hindered by an incomplete understanding of the disease progression mechanism. However, a new hypothesis postulates that many neurodegenerative diseases share a common etiology: the loss of adult neurogenesis. Disruptions in adult neurogenesis evoke substantial alterations in olfactory-, memory- and anxiety-related behaviors, strikingly similar to neurodegenerative diseases. Additionally, there is widespread loss of synaptic proteins associated with neurodegenerative diseases, however, it is largely unclear to what extent synaptic biochemistry and scaffolding are disrupted, or if immature neurons integrate properly into existing circuits. Using a transgenic neurodegenerative mouse model, we propose to identify disruption of major synaptic protein-protein interactions, the fate of newly generated neurons, and then seek to use non- invasive combined insulin/insulin growth factor 1 intranasal therapy to mitigate and prevent the onset of deficits associated with the loss of adult neurogenesis evoked by neurodegenerative diseases. This research will aid in the understanding of neurodegenerative diseases, and what are the effects of such diseases in the brain's ability to function at the most basic level. Treatment of these diseases have met with little success in recent years, therefore we will use a simple, cost-effective, non-invasive, and very safe intranasal delivery technique to treat symptoms associated with neurodegenerative diseases. Success of this research could revolutionize neurological therapy, and make safe, reliable and low-cost treatment options available to millions of people in the United States.
|Lindl, Kathryn A; Marks, David R; Kolson, Dennis L et al. (2010) HIV-associated neurocognitive disorder: pathogenesis and therapeutic opportunities. J Neuroimmune Pharmacol 5:294-309|