Hyaluronidases as Targets for Promoting Nervous System Repair in Neurodegenerative Diseases
Speaker: Professor Lawrence Sherman
Department of Cell, Developmental, and Cancer Biology
Neuroscience Graduate Program, and Graduate Program in Biomedical Sciences
Oregon Health & Science University
USA
Title: Hyaluronidases as Targets for Promoting Nervous System Repair in Neurodegenerative Diseases
Abstract: Growing evidence supports the hypothesis that insults to the central nervous system (CNS) result in dynamic changes in the extracellular matrix (ECM) that impact nervous system recovery. The Sherman lab has found that hyaluronan (HA), a mega-Dalton-sized glycosaminoglycan that is a significant component of CNS ECM, accumulates in CNS lesions following perinatal brain injury, in multiple sclerosis, in vascular brain injury accompanying Alzheimer’s disease, and following chemical insults including heavy drinking and cancer chemotherapy. Prolonged neuroinflammatory signaling in these lesions results in increased expression of the Cell migration-inducing and hyaluronan-binding protein (CEMIP), which digests HA into smaller fragments. Both the loss of high molecular weight HA and the generation of specific-sized HA fragments have multiple effects in the CNS including altering neural progenitor cell maturation, dysregulation of neuron activity, and promoting ferroptosis in brain vascular endothelial cells. The Sherman lab developed novel CEMIP-inhibitors and found that they can promote remyelination in demyelinating lesions, prevent seizures in perinatal brain injuries, normalize neuron activity and cognitive function in neuroinflammatory disease, and rescue brain vascular endothelial cells from ferroptosis in models of neurodegenerative diseases. These findings indicate that insults to the CNS lead to alterations in the HA-based ECM of the CNS that can in turn profoundly impact CNS repair and recovery, and that blocking HA catabolism is a potential therapy for each of these conditions.
About Neuroscience Seminars
Neuroscience seminars at the QBI play a major role in the advancement of neuroscience in the Asia-Pacific region. The primary goal of these seminars is to promote excellence in neuroscience through the exchange of ideas, establishing new collaborations and augmenting partnerships already in place.
Seminars in the QBI Auditorium on Level 7 are held on Wednesdays at 12-1pm, which are sometimes simulcast on Zoom (with approval from the speaker). We also occassionally hold seminars from international speakers via Zoom. The days and times of these seminars will vary depending on the time zone of the speaker. Please see each seminar listed below for details.
