Excess excitatory amino acids can provoke neuronal death in the hippocampus, and the extracellular proteases tissue plasminogen activator (tPA) and plasmin (ogen) have been implicated in this death. To investigate substrates for plasmin that might influence neuronal degeneration, extracellular matrix (ECM) protein expression was examined. Laminin is expressed in the hippocampus and disappears a...

OBJECTIVE Charcot-Marie-Tooth type 2P (CMT2P) has been associated with frameshift mutations in the RING domain of LRSAM1 (an E3 ligase). This study describes families with a novel missense mutation of LRSAM1 gene and explores pathogenic mechanisms of CMT2P. METHODS Patients with CMT2P were characterized clinically, electrophysiologically, and genetically. A neuronal model with the LRSAM1 muta...

Most peripheral neuropathies are length dependent and result in distal axonal degeneration rather than loss of neuronal cell bodies. Available therapies for axonal peripheral neuropathies are designed to control painful symptoms and not to treat the underlying axonal degeneration. Many neuroprotective therapies are being developed, primarily for central nervous system disorders such as stroke o...

Cyclin-dependent kinase 5 (Cdk5) is much more than its name implies; it plays a role in neuronal migration, neurite outgrowth and degeneration. Recent evidence suggests that Cdk5 regulates neuronal adhesion and cytoskeletal dynamics.

Axon injury elicits profound cellular changes, including axon regeneration. However, the full range of neuronal injury responses remains to be elucidated. Surprisingly, after axons of Drosophila dendritic arborization neurons were severed, dendrites were more resistant to injury-induced degeneration. Concomitant with stabilization, microtubule dynamics in dendrites increased. Moreover, dendrite...

The discovery that tissue plasminogen activator can promote neuronal degeneration has uncovered a novel pathway leading to neuronal cell death and raises important issues concerning the use of tissue plasminogen activator as a thrombolytic therapy for stroke.