Role of calpains in axonal injury and degeneration

Recommended Citation Ma, Marek, "Role of calpains in axonal injury and degeneration " (2012). Publicly Accessible Penn Dissertations. Paper 544. Role of calpains in axonal injury and degeneration Axonal injury and degeneration, whether primary or secondary, contribute to the morbidity and mortality seen in many acquired and inherited central nervous system (CNS) and peripheral nervous system (PNS) disorders, such as traumatic brain injury (TBI), spinal cord injury, cerebral ischemia, neurodegenerative diseases, and demyelinating and hereditary neuropathies. The calpain family of proteases has been causally linked to many of these acute and chronic disorders. In particular, previous studies have suggested that pathologic calpain activity may be responsible for axonal dysfunction and degeneration. Even though the immediate cause of increased intra-axonal calpain activity varies, the downstream effects of calpains may be similar. To address the role of calpains in axonal injury, I have relied on two animal models: nerve transection and optic nerve stretch. First, I demonstrated that overexpression of the endogenous calpain inhibitor, calpastatin, in transgenic mice provided biochemical and morphological protection to transected PNS axons, and biochemical protection to CNS axons. I then studied the role of calpains in synaptic dysfunction i