Panjab University, India
Title: Glia: A Real Culprit of Neuronal Vulnerability in Alzheimer's disease
Smriti Gupta has research focus on glial-neuronal crosstalk to understand the pathophysiology of Alzheimer’s disease using glial-neuronal coculture (cellular) as well as in vivo model system. This study involves the metabolic basis behind the etiology of sporadic Alzheimer’s disease and provides the pathophysiological status of different metabolic pathways such as insulin signaling pathway, glucose uptake and cerebral energy homeostasis. Research findings indicated that under disease condition, glial cells make neuronal cells more vunerable for disease onset and progression. This study provided the clue for several potential molecules which can be considered as potential therapeutic targets.
Sporadic Alzheimer’s disease (SAD) is a progressive neurodegenerative disorder with dysfunctional insulin signalling and energy metabolism. Growing evidence supports that impairment in brain insulin responsiveness, glucose utilization and energy metabolism may be a major cause of amyloid precursor protein mishandling. A support for this notion comes from the studies where streptozotocin (STZ) induced brain insulin resistance in murine model, resulting into the SAD like brain pathology with cognitive decline. Intriguingly in vitro models have been used to understand the metabolic basis of SAD. However mechanistic effects of brain insulin resistance on neurons and glia are not well understood. To understand the status of insulin signalling pathway, glucose uptake, glucose metabolism and energy homeostasis, STZ induced glial-neuronal co-culture model of SAD has been established. Present study suggests that glial cells are more compromised for insulin signalling than neurons. The evidence has been supported by glial activation in co-culture SAD model system. These changes were found to be correlated with amyloid deposition in this cellular model system which indicates that insulin signalling in glia may be a major regulator of amyloidogenesis in SAD brain.