Alzheimer's disease is a neurodegenerative disorder of unknown etiology. Currently there is no cure. One reason is that we don't know much about its pathophysiology. Two major hypotheses dominate the field: β-amyloid and tau hypothesis. In both models, aggregation and deposition of suspected proteins (β-amyloid or tau) causes neuronal death leading to loss of cognitive functions.
A new paper published in journal Nature belongs to tau model. In this research article, the authors showed that cis, but not trans form of phospho-tau (P-tau) protein contributes to development of Alzheimer-like tauopathy during traumatic brain injury that could be reversed by anti-cis antibody immunotherapy.
Here, using mouse model of traumatic head injury, the authors showed that chronic repetitive head injury caused widespread cis P-tau appearance in the brain.
Next, the authors showed that brain lysates prepared from chronically injured brain tissue could induce in vitro neuronal death that could be prevented by anti-cis antibody.
Similarly, the authors showed anti-cis antibody could reverse neuronal cell death following hypoxia or serum deprivation.
More importantly, mice treated in vivo with anti-cis antibody showed significant reduction of tau protein expression in brain tissue after brain injury.
Mechanistically, the authors hypothesized that anti-cis antibody are taken up by neurons via Fcγ receptors, internalized and interact with intracellular FcR TRIM21 that leads to tau protein detection and its elimination by proteasomal degradation.
However, it is not clear how anti-cis antibody is able to reach neurons, to begin with. BBB is not easily accessible to antibodies.
David Usharauli
A new paper published in journal Nature belongs to tau model. In this research article, the authors showed that cis, but not trans form of phospho-tau (P-tau) protein contributes to development of Alzheimer-like tauopathy during traumatic brain injury that could be reversed by anti-cis antibody immunotherapy.
Here, using mouse model of traumatic head injury, the authors showed that chronic repetitive head injury caused widespread cis P-tau appearance in the brain.
Next, the authors showed that brain lysates prepared from chronically injured brain tissue could induce in vitro neuronal death that could be prevented by anti-cis antibody.
Similarly, the authors showed anti-cis antibody could reverse neuronal cell death following hypoxia or serum deprivation.
More importantly, mice treated in vivo with anti-cis antibody showed significant reduction of tau protein expression in brain tissue after brain injury.
Mechanistically, the authors hypothesized that anti-cis antibody are taken up by neurons via Fcγ receptors, internalized and interact with intracellular FcR TRIM21 that leads to tau protein detection and its elimination by proteasomal degradation.
However, it is not clear how anti-cis antibody is able to reach neurons, to begin with. BBB is not easily accessible to antibodies.
David Usharauli
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