Everything in moderation: excessive nerve cell pruning leads to disease
Mechanism meant to maintain efficiency of brain network involved in neurodegenerative disease
Scientists at the Montreal Neurological Institute and Hospital-The Neuro, 看片视频 University, have made important discoveries about a cellular process that occurs during normal brain development and may play an important role in neurodegenerative diseases. The study鈥檚 findings, published in Cell Reports, a leading scientific journal, point to new pathways and targets for novel therapies for 础濒锄丑别颈尘别谤鈥檚, 笔补谤办颈苍蝉辞苍鈥檚, ALS and other neurodegenerative diseases that affect millions of people world-wide.
Research into neurodegenerative disease has traditionally concentrated on the death of nerve cell bodies. However, it is now certain that in most cases that nerve cell body death represents the final event of an extended disease process. Studies have shown that protecting cell bodies from death has no impact on disease progression whereas blocking preceding axon breakdown has a significant benefit. 聽The new study by researchers at The Neuro shifts the focus to the loss or degeneration of axons, the nerve-cell 鈥榖ranches鈥� that receive and distribute neurochemical signals among neurons.
During early development, axons are pruned to ensure normal growth of the nervous system. Emerging evidence suggests that this pruning process becomes reactivated in neurodegenerative disease, leading to the aberrant loss of axons and dendrites. Axonal pruning in development is significantly influenced by proteins called caspases. 鈥淭he idea that caspases are even involved in axonal degeneration during development is very recent鈥� said Dr. Philip Barker, a principal investigator at The Neuro and senior author of the study.
Dr. Barker and his colleagues show that the activity of certain 鈥檈xecutioner鈥� caspases (caspase-3 and caspase-9) induce axonal degeneration and that their action is suppressed by a protein termed XIAP (X-linked inhibitor of apoptosis). 鈥淲e found that caspase-3- and -9 play crucial roles in axonal degeneration and that their activities are regulated by XIAP. XIAP acts as a brake on caspase activity and must be removed for degeneration to proceed鈥� added Dr. Barker.聽聽
This balancing act between caspases and XIAP ensure that caspases do not cause unnecessary or excessive destruction. However, this balance may shift during neurodegenerative disease. 鈥淚f we understand the pathways that regulate XIAP levels, we may be able to develop therapies that reduce caspase-dependent degeneration during neurodegenerative disease鈥�.
Contact: Anita Kar, Communications Officer, The Neuro (514) 398-3376 or anita.kar [at] mcgill.ca
The Neuro
The Montreal Neurological Institute and Hospital 鈥� The Neuro, is a unique academic medical centre dedicated to neuroscience. Founded in 1934 by the renowned Dr. Wilder Penfield, the Neuro is recognized internationally for integrating research, compassionate patient care and advanced training, all key to advances in science and medicine. The Neuro is a research and teaching institute of 看片视频 University and forms the basis for the Neuroscience Mission of the 看片视频 University Health Centre.聽 Neuro researchers are world leaders in cellular and molecular neuroscience, brain imaging, cognitive neuroscience and the study and treatment of epilepsy, multiple sclerosis and neuromuscular disorders. For more information, visit theneuro.com