Chu Chen, Ph.D.

Keywords:
Neuroinflammation in health and disease;
Molecular and epigenetic mechanisms of neurodegenerative diseases, including
Alzheimer’s disease and traumatic brain injury (TBI)-induced AD-like neuropathology;
Endocannabinoid signaling in neuroinflammation, neuroprotection, synaptic plasticity, learning and memory;
Mechanisms of marijuana-altered synaptic and cognitive function, and cannabinoid tolerance.

Research Interests 

Inflammation is now believed to be a common mechanism of disease.  Neuroinflammation, the inflammatory response that occurs in the nervous system, has been implicated in many brain disorders, including epilepsy, traumatic brain injury, stroke, and neurodegenerative diseases such as multiple sclerosis, Parkinson’s and Alzheimer’s diseases. However, our understanding of the molecular mechanisms underlying neuroinflammation in the pathogeneses of neurodegenerative diseases is still limited.  My research programs focus on neuroinflammation in synaptic plasticity and neurodegenerative diseases.  Specifically, I am interested in endocannabinoid and prostaglandin signaling in hippocampal synaptic plasticity and pathogenesis of Alzheimer’s disease.  Recent evidence shows that a large proportion of prostaglandins derives from hydrolysis of the endogenous cannabinoid 2-arachidonoylglycerol (2-AG) by monoacylglycerol lipase (MAGL), the enzyme that primarily metabolizes 2-AG in the brain.  While 2-AG exhibits anti-inflammatory and neuroprotective properties, prostaglandins (e.g., PGE2) are proinflammatory and neurotoxic.  Therefore, MAGL plays an important role in homeostatic regulation of endocannabinoid 2-AG and prostaglandin signaling (See inset) in physiology and diseases.  Thus, inhibition of MAGL will result in strengthening anti-inflammatory and neuroprotective 2-AG signaling, while reducing proinflammatory arachidonic acid and prostaglandin levels.  We are currently addressing this important issue as to whether inactivation of MAGL is able to impromve hippocampal synaptic plasticity, learning and memory and reduce neuropathology of Alzheimer’s disease and whether epigenetic mechanisms such as noncoding small RNAs (miRNAs) are involved in regulation of synaptic plasticity and neuropathology by endocannabinoid and prostaglandin signaling.