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EMMPRIN, an upstream regulator of MMPs, in CNS biology
Deepak Kumar Kaushik1, Jennifer Nancy Hahn1, V Wee Yong1
1Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.
Abstract:
Matrix metalloproteinases (MMPs) are engaged in pathologies associated with infections, tumors, autoimmune disorders and neurological dysfunctions. With the identification of an upstream regulator of MMPs, EMMPRIN (Extracellular matrix metalloproteinase inducer, CD147), it is relevant to address if EMMPRIN plays a role in the pathology of central nervous system (CNS) diseases. This would enable the possibility of a more upstream and effective therapeutic target. Indeed, conditions including gliomas, Alzheimer's disease (AD), multiple sclerosis (MS), and other insults such as hypoxia/ischemia show elevated levels of EMMPRIN which correlate with MMP production. In contrast, given EMMPRIN's role in CNS homeostasis with respect to regulation of monocarboxylate transporters (MCTs) and interactions with adhesion molecules including integrins, we need to consider that EMMPRIN may also serve important regulatory or protective functions. This review summarizes the current understanding of EMMPRIN's involvement in CNS homeostasis, its possible roles in escalating or reducing neural injury, and the mechanisms of EMMPRIN including and apart from MMP induction.
Insights
Extracellular matrix metalloproteinase inducer (EMMPRIN) is implicated in central nervous system (CNS) diseases. This review explores EMMPRIN
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Matrix metalloproteinases (MMPs) are crucial in various pathologies.
- EMMPRIN (Extracellular matrix metalloproteinase inducer, CD147) is an upstream regulator of MMPs.
- The role of EMMPRIN in central nervous system (CNS) diseases requires investigation for potential therapeutic targeting.
Purpose of the Study:
- To review EMMPRIN's involvement in CNS homeostasis.
- To explore EMMPRIN's dual role in potentially escalating or reducing neural injury.
- To elucidate EMMPRIN's mechanisms, including and beyond MMP induction.
Main Methods:
- Literature review of studies on EMMPRIN and CNS diseases.
- Analysis of EMMPRIN's function in regulating monocarboxylate transporters (MCTs).
- Examination of EMMPRIN's interactions with adhesion molecules like integrins.
Main Results:
- Elevated EMMPRIN levels correlate with MMP production in CNS conditions like gliomas, Alzheimer's disease, and multiple sclerosis.
- EMMPRIN plays a role in CNS homeostasis, regulating MCTs and integrin interactions.
- EMMPRIN may have both detrimental and protective functions in neural injury.
Conclusions:
- EMMPRIN is a significant factor in CNS pathologies and homeostasis.
- Understanding EMMPRIN's multifaceted roles is key to developing novel CNS therapies.
- Targeting EMMPRIN upstream of MMPs offers potential therapeutic advantages.
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