Clin Transl Med: First discovery of a gradual freezing compound

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that quickly paralyzes victims.

Scientists at Northwestern University have discovered for the first time a compound that eliminates the continued degeneration of upper motor neurons.

At first, Silverman, a professor of chemistry at Nishimoto University, discovered a compound NU-9 that can reduce protein misfolding in key cell lines.

The upper motor neuron is the commander-in-chief of brain movement.

In ALS, motor-initiating nerve cells in the brain (upper motor neurons) and muscles in the spinal cord control nerve cells (lower motor neurons) to die.

NU-9 treatment can improve the ultrastructural integrity of mitochondria and upper motor neurons ( UMNs ) and endoplasmic reticulum ( ER )

NU-9 treatment can improve the cellular structural integrity of the disintegration of the root tip dendrites of upper limb motor neurons ( UMN )

NU - 9 treatment can reduce the degeneration of UMN 's upper motor neuron ( UMN ) that is caused by SOD1 in vivo toxic misfolding

Research and analysis show that NU-9 has similar drug-like pharmacokinetic properties, can improve the structural integrity of mitochondria and ER, reduce the level of mSOD1, stabilize the degraded UMN apical dendrites, and improve the exercise behavior measured by the thread-hanging test.

The results showed that the mechanism-centric and cell-based drug discovery method not only solved the key cell defect that caused UMN loss, but also discovered NU-9, the first compound to improve the health of diseased UMNs.

Hande Ozdinler, associate professor of neurology at Northwestern University School of Medicine, said that even though upper motor neurons are responsible for the initiation and regulation of exercise, their degeneration is an early event of ALS, but so far, there is no treatment plan to improve their health.

In fact, the NU-9 compound solves two important factors that cause upper motor neuron disease in ALS: protein misfolding and protein clumps in the cell .

After NU-9 was given, both mitochondria and endoplasmic reticulum began to restore their health and integrity, thereby improving the health of neurons.

The scientists next conducted experiments to reveal how and why the diseased upper motor neurons recovered health.

Original source:

Barış Genç, Mukesh Gautam, Öge Gözütok, Ina Dervishi, Santana Sanchez, Gashaw M.