Kiran Bhaskar, Ph.D.
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JAD profile
Affiliation(s):
University of New Mexico
ORCID URL:
Areas of Interest:
Alzheimer's disease, tauopathies, dementia, neuroinflammation
Biography & Research:
Regulation of Alzheimer’s disease tau pathology by the microglia-specific neuroinflammation. Prominent filamentous inclusions of microtubule-associated protein tau (MAPT) and neurodegeneration are hallmarks of many neurodegenerative tauopathies including Alzheimer's disease (AD). Although the exact etiology of many of these tauopathies remains elusive, neuropathologically they are characterized by intracellular aggregates of hyperphosphorylated MAPT, neuroinflammation and cell death. Increasing evidence suggests that neuroinflammation may directly contribute to the pathophysiology of neurodegenerative tauopathies. We have recently provided compelling evidence that neuroinflammation, cell-autonomous to microglia, accelerates MAPT phosphorylation, aggregation and behavioral impairment in a mouse model of tauopathy (hTau). Notably, the effects of microglial activation on MAPT pathology were enhanced when mice were deficient for the microglial-specific fractalkine receptor, CX3CR1. We also demonstrated that interleukin-1 (IL-1) released by reactive microglia induces MAPT phosphorylation in primary neurons via activating neuronal IL-1 receptor (IL-1R) and p38 mitogen-activated protein kinase (p38 MAPK) pathway. We are currently investigating whether blocking IL-1-p38 MAPK-MAPT pathway via pharmacological or genetic means would prevent MAPT pathology, neurodegeneration and improve cognitive function in various models of tauopathy.
