Friday, November 12, 2021

Blocking tau may help ALS patients

Good news! Are we finally making progress on ALS?

"... Studies of Alzheimer’s disease also have linked changes in mitochondrial function to interactions between an abnormal form of tau, which accumulates in the brains of Alzheimer’s patients, and a mitochondrial protein called dynamin-related protein 1. ... examined whether these interactions might also promote mitochondrial dysfunction in ALS, and whether reducing tau could be a novel and promising therapeutic approach to fight the disease. Using brain tissue from dead ALS patients, the team found the abnormal form of tau in brain in places where tau is not normally found. When cells were grown in contact with deceased ALS patients’ brain tissue that contained abnormal tau, the cells’ mitochondria fragmented and oxidative stress increased. Importantly, reducing tau with a specific degrader reversed these effects, reducing mitochondrial fragmentation and lowering oxidative stress.
“We demonstrated for the first time that targeting tau with a new class of small molecules that selectively degrade it can reverse the ALS-induced changes in mitochondria’s shape and function ..."

From the abstract:
"... Lastly, reducing tau levels with QC-01-175, a selective tau degrader, prevented ALS SNs-induced mitochondrial fragmentation and oxidative stress in vitro. Collectively, our findings suggest that increases in pTau-S396 may lead to mitochondrial fragmentation and oxidative stress in ALS and decreasing tau may provide a novel strategy to mitigate mitochondrial dysfunction in ALS."

Blocking tau, an Alzheimer’s hallmark, may help ALS patients – Harvard Gazette

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