The Molecular Neuroscience Laboratory focuses on tau metabolism and tau pathogenesis in Alzheimer disease (AD) and related neurodegenerative diseases.
Tau is a major microtubule-associated protein that is mainly present in neurons. The biological function of tau is to stimulate microtubule assembly and to stabilize microtubules. Microtubules are a component of the cytoskeleton involved in maintaining the structure of cells. Tau can be abnormally modified by phosphate groups and aggregated as neurofibrillary tangles in the brains of individuals with AD, Down syndrome (DS), and related neurodegenerative disorders. Normal adult human brain expresses six variants of tau generated by the alternative splicing of exons 2, 3, and 10 of its pre-mRNA. Dysregulation of tau exon 10 splicing has been seen in several neurodegenerative diseases.
This laboratory is investigating the molecular mechanisms leading to altered brain molecular pathways during neurodegeneration, with a focus on tau metabolism, including transcription of tau pre-mRNA from DNA, alternative splicing of tau pre-mRNA, tau mRNA stability, translation of tau from the mRNA, tau protein modifications, and degradation of tau as well as tau propagation in AD and DS brain.
Studies carried out in this laboratory may help identify new strategies for the prevention and treatment of AD, DS, and related neurodegenerative disorders.