Ask your competent? doctor if anything here is worth exploring for stroke recovery. DO NOT ACCEPT ANY ANSWER LESS THAN: 'We'll look into it by contacting researchers for more research.'! Not doing that is a complete sign of incompetence!
KCNJ2 inhibition mitigates mechanical injury in a human brain organoid model of traumatic brain injury
Highlights
- •Mechanically injured organoids display hallmark features of traumatic brain injury
- •TDP-43 dysfunction is a key driver of acute injury and is enhanced in ALS/FTD
- •A CRISPRi screen identifies KCNJ2 inhibition as a therapeutic target in vitro
- •Kcnj2 knockdown in mice reduces TDP-43 pathology and is protective against brain injury
Summary
Traumatic
brain injury (TBI) strongly correlates with neurodegenerative disease.
However, it remains unclear which neurodegenerative mechanisms are
intrinsic to the brain and which strategies most potently mitigate these
processes. We developed a high-intensity ultrasound platform to inflict
mechanical injury to induced pluripotent stem cell (iPSC)-derived
cortical organoids. Mechanically injured organoids elicit classic
hallmarks of TBI, including neuronal death, tau phosphorylation, and
TDP-43 nuclear egress. We found that deep-layer neurons were
particularly vulnerable to injury and that TDP-43 proteinopathy promotes
cell death. Injured organoids derived from C9ORF72 amyotrophic
lateral sclerosis/frontotemporal dementia (ALS/FTD) patients displayed
exacerbated TDP-43 dysfunction. Using genome-wide CRISPR interference
screening, we identified a mechanosensory channel, KCNJ2, whose
inhibition potently mitigated neurodegenerative processes in vitro and in vivo, including in C9ORF72
ALS/FTD organoids. Thus, targeting KCNJ2 may reduce acute neuronal
death after brain injury, and we present a scalable, genetically
flexible cerebral organoid model that may enable the identification of
additional modifiers of mechanical stress.
00085-7&id=fx1.jpg){kind=link}
No comments:
Post a Comment