Tau alternative splicing and frontotemporal dementia.
A number of neurodegenerative diseases are characterized by the presence of abundant deposits containing Tau protein. Expression of the human tau gene is under complex regulation. Mutations in the tau gene have been identified in patients with frontotemporal lobe dementia. These mutations affect either biochemical/biophysical properties or the delicate balance of different splicing isoforms. In this review, we summarize recent advances in our understanding of genetics and molecular pathogenesis of tauopathies with the focus on frontotemporal lobe dementia. We review published studies on tau pre-mRNA splicing regulation. Understanding molecular mechanisms of tauopathies may help in developing effective therapies for neurodegenerative tauopathies and related disorders, including Alzheimer disease.
Kar
Amar
A
Center for Molecular Neuroscience, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Kuo
David
D
He
Rongqiao
R
Zhou
Jiawei
J
Wu
Jane Y
JY
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020774:Pick Disease of the Brain / Q000235:genetics* / Q000473:pathology; D016875:tau Proteins
C054369:MAPT protein, human; D009419:Nerve Tissue Proteins; D016875:tau Proteins