The Rao laboratory in the CDR is interested in understanding the mechanisms involved in degeneration of neurons in the brain by proteases elevated in Alzheimer’s disease.
We have developed mouse models to inhibit specific proteases and using these models we are studying protease inactivation as a potential AD therapy.
We are also studying ALS with the same inhibitor model to develop a therapy.
These studies focus on how the cytoskeleton of the neuron is disrupted by proteases and the molecular mechanisms that lead to destabilization and death of neurons.
Dr. Mala Rao’s work in the CDR resulted in the development of a new mouse model to study AD (Rao et al., J. Neuroscience, 2008) that has demonstrated proof of concept for the use of selective inhibitors of calpains, a class of proteases, as therapies in several neurodegenerative diseases, including AD and ALS.
Axonal Transport
Dr. Rao’s laboratory is also interested in understanding how the cellular transport is regulated in neurons.
Our recent discovery that Myosin Va motor (Myo Va) binds to the rod domain of NF-L suggests that Myo Va may use NFs as tracks for the translocation of organelles in the large axons where microtubule and actin networks are in small numbers. These studies propose novel model for the axonal transport of organelles in axons (Rao et al., PLoS ONE, 2011).
Rao’s lab is also interested in understanding the role of NFs in regulating various cellular processes such as axonal transport, memory and proteolysis using mouse mutants of neurofilament subunit genes.
Calpain Inhibition
Dr. Rao’s laboratory has been investigating the effect of calpain protease inhibitor, calpastatin, in degeneration of motor axons in ALS model.
Dr. Rao’s effort was awarded with a 2 year grant from NIH/NINDS to examine effects of calpain inhibitor on disease onset and progression in ALS mouse model and also a NIH/NIA grant to examine role of cytoskeletal proteolysis in aging brain for 5 years.