Liu M.C.,Banyan Biomarkers, Inc.
Axonally specific microtubule-associated protein tau is an important component of neurofibrillary tangles found in AD (Alzheimer's disease) and other tauopathy diseases such as CTE (chronic traumatic encephalopathy). Such tau aggregate is found to be hyperphosphorylated and often proteolytically fragmented. Similarly, tau is degraded following TBI (traumatic brain injury). In the present study, we examined the dual vulnerability of tau to calpain and caspase-3 under neurotoxic and neurodegenerative conditions. We first identified three novel calpain cleavage sites in rat tau (four-repeat isoform) as Ser130↓Lys131, Gly157↓Ala158 and Arg380↓Glu381. Fragment-specific antibodies to target the major calpain-mediated TauBDP-35K (35 kDa tau-breakdown product) and the caspase-mediated TauBDP-45K respectively were developed. In rat cerebrocortical cultures treated with excitotoxin [NMDA (N-methyl-D-aspartate)], tau is significantly degraded into multiple fragments, including a dominant signal of calpain-mediated TauBDP-35K with minimal caspase-mediated TauBDP-45K. Following apoptosis-inducing EDTA treatment, tau was truncated only to TauBDP-48K/45K-exclusively by caspase. Cultures treated with another apoptosis inducer STS (staurosporine), dual fragmentation by calpain (TauBDP-35K) and caspase-3 (TauBDP-45K) was observed. Tau was also fragmented in injured rat cortex following TBI in vivo to BDPs of 45-42 kDa (minor), 35 kDa and 15 kDa, followed by TauBDP-25K. Calpain-mediated TauBDP-35K-specific antibody confirmed robust signals in the injured cortex, while caspase-mediated TauBDP-45K-specific antibody only detected faint signals. Furthermore, intravenous administration of a calpain-specific inhibitor SNJ-1945 strongly suppressed the TauBDP-35K formation. Taken together, these results suggest that tau protein is dually vulnerable to calpain and caspase-3 proteolysis under different neurotoxic and injury conditions. Source
Banyan Biomarkers, Inc. | Date: 2013-07-22
The present invention identifies biomarkers that are diagnostic of neural injury, neuronal disorder or neurotoxicity and is related to the discovery that proteases are selectively activated in subjects suffering from nervous system damage as compared to healthy subjects. Breakdown products reflecting protease activation are produced and detection of these different biomarkers of the invention is also diagnostic of the degree of severity and type of nerve damage in a subject.
Banyan Biomarkers, Inc. | Date: 2014-03-17
The present invention relates to an exemplary in vitro diagnostic (IVD) device used to detect the presence of and/or severity of neural injuries or neuronal disorders in a subject. The IVD device relies on an immunoassay which identifies biomarkers that are diagnostic of neural injury and/or neuronal disorders in a biological sample, such as whole blood, plasma, serum, cerebrospinal fluid (CSF). The inventive IVD device may measure one or more of several neural specific markers in a biological sample and output the results to a machine readable format wither to a display device or to a storage device internal or external to the IVD.
Banyan Biomarkers, Inc. | Date: 2014-03-17
An in vitro diagnostic (IVD) device is used to detect the presence of and/or severity of liver injury in a subject. The IVD device relies on an immunoassay which identifies biomarkers that are diagnostic of liver injury in a biological sample, such as whole blood, plasma, serum. The inventive IVD device may measure one or more of several specific markers in a biological sample and output the results to a machine readable format wither to a display device or to a storage device internal or external to the IVD.
Banyan Biomarkers, Inc. | Date: 2013-07-10
Severe traumatic brain (TBI) injuries are often associated with long-term and disabling consequences. Prognosis and chronic treatment planning following severe TBI remain challenging. The discovery of specific brain biomarkers could create new opportunities for more accurate clinical assessments identifying groups that may experience better outcomes when exposed to an intervention. The present invention provides a method of detection of Microtubule-associated protein-2 (MAP-2), a marker of dendritic damage, in a biological sample of survivors after TBI and evaluates the recovery of the patient, including an improvement in cognitive abilities and function.