Analysis of the Calpain Pathway in Cerebral Ischemia

Calpain is an enzyme that hydrolyzes proteins and is highly expressed in the central nervous system. During cerebral ischemia, intracellular calcium levels increase dramatically due to excitotoxicity, which leads to the activation of several proteases, including calpain. In animal models of cerebral ischemia, inhibition of calpain has been shown to be neuroprotective and able to reduce neuronal damage caused by this pathology. On the other hand, after stroke, neural stem cell (NSC) proliferation increases and newly formed neuroblasts migrate toward the site of injury. However, the process of forming new neurons after injury is not efficient, and finding ways to improve it may help recovery after injury. Thus, understanding the role of calpain in neurogenesis may open new windows for the treatment of stroke.

Fig. 1. Calpain mediates excitotoxicity via protein cleavage. (Lai et al., 2014)

Our Services

Ace Therapeutics is a leading company in the field of stroke research, providing comprehensive analytical services for studying the calpain pathway in cerebral ischemia. Our team of expert biologists and neuroscientists utilize cutting-edge technology and state-of-the-art equipment to provide accurate and reliable data for understanding the molecular mechanisms of the pathway. We aim to help our clients develop NMDAR agonists leading to calpain activation as a neuronal damage pathway and therapeutic target in ischemic stroke.

Analysis of Pathogenic Activation of Calpain in Stroke

We offer highly sensitive enzyme activity assays to measure the protein hydrolyzing activity of calpain in brain samples. By assessing calpain activity, we can evaluate the extent of calpain-mediated protein hydrolysis and its effect on neuronal damage in cerebral ischemia.

Molecular Interactions and Signaling Pathways Analysis

To understand the complex regulatory network of the calpain pathway, Ace Therapeutics employs advanced techniques (immunoprecipitation and mass spectrometry) to study molecular interactions and signaling pathways associated with calpain activation in cerebral ischemia, including but not limited to:

• NMDAR：GluN1, GluN2A, and GluN2B subunits
• Metabotropic glutamate receptor 1 (mGluR1)
• CRMP2
• p25/cell cycle protein-dependent kinase 5 (CDK5) death signaling pathway
• Tau protein
• Methionine aminopeptidase 2 (MetAP2)
• p38 MAPK signaling pathway
• Pro-cell survival proteins such as tyrosine kinase Src, PSD-95, and Kidins220
• Striatal-enriched protein tyrosine phosphatase (STEP) signaling pathway

Effects Assessment of Calpain on Neurogenesis

Prospective therapies targeting calpain activity may improve the formation of new neurons after stroke. We can investigate the role of calpain in neural stem cell proliferation and neuroblast migration in two neurogenic regions in the mouse brain, the dentate gyrus (DG) and the subventricular zone (SVZ).

With our expertise, state-of-the-art facilities, and collaborative approach, Ace Therapeutics is committed to helping clients explore new direction for the treatment of ischemic stroke by targeting the calpain pathway. If you are interested in our services, please do not hesitate to contact us!

1. Lai, T. W., et al. (2014). Excitotoxicity and stroke: identifying novel targets for neuroprotection. Progress in neurobiology, 115, 157-188.