Title : Cerebral vascular calcium signaling in diabetic Alzheimer's disease-related dementias
Alzheimer’s disease (AD) and AD-related dementias (ADRD) are the common incurable neurodegenerative conditions characterized by progressive cognitive deterioration, memory decline and even death. The major forms of ADRD include vascular contributions to cognitive impairment and dementia (VCID). In agreement, vascular dementia is the second most common form of dementia and the most frequent comorbidity with AD. Diabetes is a leading factor in the development of VCID. The molecular mechanisms that link diabetes to the development of VCID remain to be elucidated, and the current treatments for these diseases are neither always effective nor specific. We and other investigators have found that the severity of diabetes is highly associated with the cognitive and memory impairments. The role of diabetes may primarily occur due to the abnormal glucose metabolism and increased reactive oxygen species (ROS) production in cerebral vascular smooth muscle cells (CASMCs). In support, antioxidant therapies have shown promising results in protecting against diabetes-induced VCID and other dementias. Diabetes increases mitochondrial ROS. The increased mitochondrial ROS could dissociate FK506 binding protein 12.6 (FKBP12.6) from type-2 ryanodine receptor (RyR2) to remove its inhibitory effect on RyR2 channel and induce Ca2+ release, which causes cerebral vasoconstriction and cerebral blood flow reduction, thereby leading to progressive memory loss, cognitive decline and VCID. These novel findings may not only enhance our understanding of the molecular mechanisms for VCID, ADRD and AD, but also help to identify novel therapeutic targets for these common devastating diseases.
What will audience learn from your presentation?
- Our current presentation will greatly help the audience to create their future research directions
- The finding presented may significantly assist the audience to develop new drugs, establish novel preventive and therapeutic strategies for VCID and other dementias.
- Our research could also be used by other faculty to expand their research or teaching.