Aggravating Aggregates — In the June 26, 2013 issue of the Journal of Neuroscience, Dr. Steven Walkley and recent Einstein Ph.D. graduate Dr. Matthew Micsenyi published their finding of a disease-causing mechanism for late-infantile Batten disease, a rare disorder of toddler-aged children that results in mental and physical deterioration, seizures, vision loss and, ultimately, premature death. This type of Batten disease is caused by a genetic deficiency in an enzyme, tripeptidyl peptidase I, which normally breaks down proteins within cellular compartments (lysosomes) where digestion of cellular debris takes place. The researchers discovered a breakdown of the lysosomal membrane, a process called lysosome membrane permeability (LMP), caused abnormal protein accumulation in brain cells. Notably, LMP stimulated a response by the macroautophagy adapter protein p62, whereby p62 surrounded damaged lysosomes within a shell-like structure. There is currently no treatment for Batten disease; this work identifies LMP as a possible target for developing therapeutics, which also might be applied to other protein aggregate-related diseases, such as Huntington's and Parkinson's diseases. Dr. Walkley is professor of neuroscience, of pathology, and of neurology and director of the Rose F. Kennedy Intellectual and Developmental Disabilities Research Center.
Posted on: Monday, July 22, 2013