Analysis of MMP Signaling Pathway in Stroke

Matrix metalloproteinases (MMPs) are endopeptidases involved in physiological processes in the brain, maintaining the integrity of the blood-brain barrier and playing a key role in cerebral ischemia. During the acute phase of stroke activity, MMP expression is increased and associated with adverse effects. However, MMP facilitates the healing process by remodeling tissue damage in the post-stroke phase. In addition, adverse effects of tissue plasminogen activator (tPA) are mediated by MMPs, which increases BBB permeability by degrading extracellular matrix (ECM) and tight junction (TJ) components in endothelial cells (EC).

Fig. 1. Mechanisms in MMP activation leading to degradation of extracellular matrix and blood-brain barrier disruption/hemorrhage. (Lakhan et al., 2013)

Our Services

Ace Therapeutics offers comprehensive services to analyze the precise role of MMPs after stroke and discover MMPs as therapeutic targets for stroke. Our state-of-the-art laboratory facilities and team of expert researchers help clients perform comprehensive and accurate assessments of MMP expression, activity, and localization in in vitro and animal models of stroke. We aim to advance their stroke diagnostic and therapeutic development strategies for MMPs.

How Do We Analyze the Role of MMPs in Stroke?

• We can analyze the regulation of BBB permeability and function by multiple MMPs (MMP-2 and MMP-9) in middle cerebral artery occlusion (MCAO) models, focusing on the expression levels of proteins such as ZO-1, claudin-1, claudin-5, and occludin.
• We can analyze the association between oxidative stress and MMP by detecting MMP-2 and -9 activities in animal models of ischemic stroke.
• We use tissue inhibitor of metalloproteinase (TIMP) knockout (KO) and MCAO mouse models to analyze the relationship between MMP and neuroinflammation. We can detect MMP-3 and -9 activities in neurons, astrocytes, and microglia, as well as the expression of pro-inflammatory cytokines (e.g., tumor necrosis factor TNF-α, interleukin IL-1β, IL-6, and IL-18).

Development of Stroke Drugs Targeting MMPs

MMP has been explored as a potential therapeutic target due to its beneficial and deleterious roles in stroke. Our experts are committed to developing MMPs as potential targets for pharmacologic intervention in stroke. Through careful structure-based drug design and rigorous preclinical testing, we help clients develop stroke drugs that target MMPs.

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

1. Lakhan, S. E., et al. (2013). Matrix metalloproteinases and blood-brain barrier disruption in acute ischemic stroke. Frontiers in neurology, 4, 32.