NK1 receptor antagonists (substance P blockers) reduced tau phosphorylation — a hallmark of CTE — after both blast and repeated concussive brain injuries in mice, offering a potential preventive therapy.
Tau phosphorylation prevented across 3 TBI modelsNK1 antagonists modulated key kinases (Akt, ERK1/2, JNK) downstream of substance P release
What the researchers found
NK1 receptor antagonists attenuated tau hyperphosphorylation after blast and concussive TBI by modulating Akt, ERK1/2, and JNK kinases, with the mechanism initiated by TRPV1 mechanoreceptor-mediated substance P release.
Why it matters
CTE is a devastating neurodegenerative disease affecting athletes and military personnel with no prevention or treatment. Identifying that substance P mediates the initial tau pathology opens a potentially practicable therapeutic window for preventing CTE after known head injuries.
The numbers in context
3 TBI models; NK1 antagonist reduced p-tau; modulated Akt, ERK1/2, JNK; TRPV1 inhibitor effective pre-injury only
How the study worked
Mouse models of single moderate TBI, repeated concussive TBI, and blast-induced mild TBI. Post-injury NK1 antagonist or pre-injury TRPV1 inhibitor treatment. Tau phosphorylation analysis, kinase activity assessment, and neurological outcome testing.
Who was studied
Rats with single moderate TBI, repeated concussive TBI, or blast-induced mild TBI
What this study cannot tell us
Mouse study — TBI models may not perfectly replicate human concussions or blast exposure. Post-injury treatment timing and duration for optimal effect not fully established. Long-term CTE prevention not demonstrated (only acute tau phosphorylation).
How to read the evidence
Well-designed preclinical study with multiple TBI models and mechanistic validation. Strong translational potential given existing FDA-approved NK1 antagonists.
When this study was published
Published in 2021 in Scientific Reports, providing a mechanistic link between substance P and CTE-related tau pathology.
The bigger picture
CTE has gained enormous attention as a cause of cognitive decline and behavioral changes in athletes and veterans, but no preventive treatment exists. This study identifies a druggable pathway — substance P/NK1R — and suggests that existing NK1 antagonists (already FDA-approved for other uses) could potentially be repurposed to prevent CTE after head injuries.
Questions still open
- Could NK1 antagonists be given to athletes or soldiers after head injuries to prevent CTE?
- What is the therapeutic window for NK1 antagonist treatment after TBI?
- Would long-term NK1 antagonist use prevent the full cascade of CTE development?
Common questions
Could a drug prevent CTE after head injuries?
How does a head injury lead to CTE?
Read the original research
NK1 antagonists attenuate tau phosphorylation after blast and repeated concussive injury.
Scientific reports, 11(1), 8861
Citation
Corrigan, Frances; Cernak, Ibolja; McAteer, Kelly; Hellewell, Sarah C; Rosenfeld, Jeffrey V; Turner, Renée J; Vink, Robert. (2021). NK1 antagonists attenuate tau phosphorylation after blast and repeated concussive injury.. Scientific reports, 11(1), 8861. https://doi.org/10.1038/s41598-021-88237-0