Self-Corrective Mechanism at Synapse Doubles Lifespan in Mouse Model of ALS (Lou Gehrig’s Disease), Suggests New Approach to Therapy for Human Brain Diseases

A common feature of neurodegenerative diseases such as Alzheimer’s disease and amyotrophic lateral sclerosis (ALS) (also called Lou Gehrig’s disease) is the progressive loss of synapses – the anatomical sites of communication between brain cells – throughout the brain and spinal cord. Typically, synapse loss becomes pervasive before the outward appearance of symptoms of disease, such as memory loss or paralysis. The fact that there must be extensive synapse loss before brain function begins to seriously decline suggests that the nervous system maintains a deep functional reserve that keeps everything working normally until the damage passes a tipping point and the brain’s resilience begins to break down. But how exactly does this functional reserve confer resilience in the face of ongoing brain degeneration? Could differences in this reserve explain why some individuals with ALS decline and die within months, while others – like astrophysicist Steven Hawking (photo)--live for decades? And could a treatment that boosts this functional reserve help more patients survive and prosper as long as Hawking? In a new study, published online on May 6, 2020 in Neuron (, University of California San Francisco (UCSF) neuroscientist Graeme Davis, PhD, and his team have identified a powerful self-corrective mechanism within synapses that is activated by neurodegeneration and acts to slow down disease progression in animal models of ALS. Selectively eliminating this self-corrective mechanism dramatically accelerated progression of ALS in mice, shortening their lifespan by 50 percent.
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