Rao Lab

Head of Lab

Mala Rao , PhD

Neurodegenerative Mechanisms in Alzheimer’s Disease and Amyotrophic Lateral Sclerosis

Dr. Rao and colleagues in the Rao Lab, address molecular mechanisms of neuron cell death in AD and amyotrophic lateral sclerosis (ALS), focusing on multiple proteolytic systems in neurons that serve as initiators and executioners of cell death programs relevant to brain disease. A particular interest is the calpain protease system activated in various neurological conditions and an important disease target. Our investigations of calpastatin, a highly specific natural inhibitor of calpains, as a proof-of-principal therapy have demonstrated striking alleviation of disease symptoms and life extension in models of AD, tauopathy, Huntington disease, Parkinson’s disease, and ALS, which has strongly encouraged the global search for specific small-molecule calpain inhibitors. Investigations on calpains and autophagy in relation to axonal transport and metabolism of cytoskeletal proteins, especially neurofilament proteins, have uncovered key mechanisms regulating axonal and synaptic function in the healthy brain and defined consequences for motor and cognitive function of these disease-related proteolytic disruptions.

Dr. Mala Rao’s work in the CDR has 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.

Dr. Rao’s laboratory is also interested in understanding how the cellular transport is regulated in neurons. Our 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.

Publications

All publications

Rao lab members

Chunfeng Huo, BA - Research Technician