The McConlogue laboratory focuses on both understanding the mechanisms involved in neurodegeneration driven by misfolding-prone proteins and in developing therapeutic approaches to treat neurological diseases such as Alzheimer's and Parkinson's diseases (AD and PD) and Lewy body dementias (LBD). We are particularly interested in understanding the pathogenic role and functional perturbation of intrinsically disordered proteins (IDP) that, due to their unique structural characteristics and key functional roles, lead to diseases of amyloid-type misfolding including cancer and neurodegenerative diseases.
Our current focus is on understanding and blocking the pathogenic processes of alpha-Synuclein (a-Syn), an IDP that plays a central role in PD and LBD and also contributes to AD. Specifically we are identifying both small molecule and cellular chaperones that protect against a-Syn pathogenicity and investigating their mechanisms of action. We have identified a novel action of the cellular chaperone Hsp70 preventing pathogenic a-Syn misfolding using a non-canonical Hsp70 engagement site. This discovery could lead to therapies for AD, PD and LBD specifically targeting Hsp70 to a-Syn without perturbing the myriad of essential proteins that are canonical substrates of Hsp70.
August 1, 2015 - July 31, 2018 - Small-Molecule Pharmacological Chaperones to Prevent Synuclein Transmission , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21NS092897
University of California, Los Angeles, B.A., 1973, Mathematics
University of California, Los Angeles, M.S., 1975, Medical Physics
University of California, Los Angeles, Ph.D., 1978, Medical Physics
University of California, San Francisco, Postdoctoral, 1985, Somatic Cell Genetics