Tissue kallikrein KLK1 and the kallikrein-related peptidases KLK2-15 are a subfamily of serine proteases that have defined or proposed roles in a range of central nervous system (CNS) and non-CNS pathologies. To further understand their potential activity in multiple sclerosis (MS), serum levels of KLK1, 6, 7, 8 and 10 were determined in 35 MS patients and 62 controls by quantitative fluorometric ELISA. Serum levels were then correlated with Expanded Disability Status Scale (EDSS) scores determined at the time of serological sampling or at last clinical follow-up. Serum levels of KLK1 and KLK6 were elevated in MS patients (p

Kallikreins (KLKs) are a family of 15 secreted serine proteases with emerging roles in neurological disease. To illuminate their contributions to the pathophysiology of spinal cord injury (SCI) we evaluated acute through chronic changes in the immunohistochemical appearance of six kallikreins, KLK1, KLK5, KLK6, KLK7, KLK8 and KLK9 in post-mortem human traumatic SCI cases, quantified their RNA expression levels in experimental murine SCI, and assessed the impact of recombinant forms of each enzyme toward murine cortical neurons in vitro. Temporally and spatially distinct changes in kallikrein expression were observed with partially overlapping patterns between human and murine SCI, including peak elevations (or reductions) during the acute and subacute periods. KLK9 showed the most robust changes and remained elevated chronically. Importantly, a subset of kallikreins, KLK1, KLK5, KLK6, KLK7 and KLK9 were shown to be neurotoxic toward primary neurons in vitro. Kallikrein immunoreactivity was also observed in association with swollen axons and retraction bulbs in the human SCI materials examined. Together, these findings demonstrate that elevated levels of a significant subset of kallikreins are positioned to contribute to neurodegenerative changes in cases of CNS trauma and disease and therefore represent new targets for the development of neuroprotective strategies.