Quercetin is a naturally occurring flavonoid, a compound present in many fruits and vegetables such as grapes, cherries, apples, onions, and broccoli.

How quercetin works

Spinal muscular atrophy (SMA) is caused by a mutation in the SMN1 gene, which encodes for the SMN protein that is essential for the survival of motor neurons, nerve cells that control muscle movement. The mutation means that not enough SMN protein is made and motor neurons die with time, causing the symptoms of SMA.

Quercetin may prevent the death of motor neurons through multiple mechanisms. It may modulate sirtuins and β-catenin, which are critical signaling proteins that regulate the survival of motor neurons.

Quercetin also possesses antioxidant properties that can reduce the accumulation of toxic reactive oxygen species that can cause the death of motor neurons.

Finally, quercetin may promote the expression of the SMN2 gene, a second gene that encodes for SMN protein, thereby reducing the severity of SMA.

Quercetin studies

The potential benefits of quercetin in patients with SMA have not yet been investigated in clinical trials, but pre-clinical studies in animal models have yielded some promising results.

Using mouse models of SMA, researchers have shown that quercetin activates SIRT1, a stress-response and chromatin silencing protein. SIRT1 is involved in various DNA-related events such as transcription, DNA replication, and DNA repair, and is generally associated with cell survival.

Gene expression studies in the fibroblast cell lines from two SMA type 1 patients have shown that quercetin upregulates the SMN2 mRNA levels four-fold. However, in this study, SMN protein levels remained unchanged.

In zebrafish and mouse models of SMA, quercetin was shown to inhibit the activation of β-catenin, which is aberrantly upregulated in nerve and muscle cells because the proteins that mark β-catenin for degradation are deficient. β-catenin signaling plays a significant role in the death of motor neurons and the atrophy of muscle tissue in SMA patients.

Clinical trials in humans are necessary to determine the safety, efficacy, and dosage of quercetin as a potential treatment for SMA.


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