The Duke study is the first to identify where the cln3 protein resides in human brain cells and to link the protein's location to its function. The researchers discovered that cln3 transports a vital lipid, or complex fat molecule, within a cell. The breakdown of this transportation system results in uncontrolled apoptosis, or cell death, and the neural degeneration that is a hallmark of Batten disease.
"Genetic diseases such as Batten disease provide a unique opportunity to understand the role of proteins, like cln3, that are vital for normal cell function," said Rose-Mary Boustany, M.D., a professor of pediatrics and neurobiology at Duke University Medical Center and senior author of the study.
The results appear in the September 2004 issue of Pediatric Research. The study was supported by the National Institute of Neurological Disorders and Stroke, a division of the National Institutes of Health.
Understanding the role of cln3 has implications beyond juvenile Batten disease a rare, untreatable disorder -- because the protein is overproduced by cells in a number of cancers. And the lipid transported by cln3 plays an important role in infection by the AIDS virus and prion proteins, and in developing Alzheimer's disease. Prions are infectious proteins that can transmit diseases such as Creutzfeld-Jacob or mad cow disease.
Batten disease collectively refers to inherited disorders also called the neuronal ceroid lipofuscinoses, or NCL, which share similar clinical and pathological traits but are genetically distinct. All NCL disorders cause progressive loss of motor skills, mental retardation, loss of speech, blindness, uncontrolled seizures and, eventually, premature death.