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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32NS067945-01
Application #
7805063
Study Section
Special Emphasis Panel (ZRG1-F01-W (22))
Program Officer
Refolo, Lorenzo
Project Start
2010-02-01
Project End
2010-10-31
Budget Start
2010-02-01
Budget End
2010-10-31
Support Year
1
Fiscal Year
2010
Total Cost
$36,079
Indirect Cost
Name
University of Pennsylvania
Department
Pathology
Type
Schools of Dentistry
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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