New details learned about a key cellular protein could lead to treatments for neurodegenerative diseases, such as Parkinson's, Huntington's, Alzheimer's, and amyotrophic lateral sclerosis (ALS). In a new study, researchers in the laboratory of Steven Finkbeiner, MD, PhD, at the Gladstone Institutes used a different protein, Nrf2, to restore levels of the disease-causing proteins to a normal, healthy range, thereby preventing cell death.

The researchers tested Nrf2 in two models of Parkinson's disease: cells with mutations in the proteins LRRK2 and α-synuclein. By activating Nrf2, the researchers turned on several "house-cleaning" mechanisms in the cell to remove excess LRRK2 and α-synuclein."Nrf2 coordinates a whole program of gene expression, but we didn't know how important it was for regulating protein levels until now"

Single protein may hold secret to treating Parkinson's disease and more | EurekAlert! Science News

Some Nfr2 activators are DHA, Gastrodin, Sulforaphane from broccoli, Pterostilbene, Curcumin, Green tea, Milk thistle, Bacopa, and Ashwagandha.

Berberine also activates Nfr2!

Berberine activates Nrf2 nuclear translocation and inhibits apoptosis induced by high glucose in renal tubular epithelial cells through a phosphatidylinositol 3-kinase/Akt-dependent mechanism.

Berberine activates Nrf2 nuclear translocation and inhibits apoptosis induced by high glucose in renal tubular epithelial cells through a phosphati... - PubMed - NCBI


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Berberine activates Nrf2 nuclear translocation and protects against oxidative damage via a phosphatidylinositol 3-kinase/Akt-dependent mechanism in NSC34 motor neuron-like cells.
Abstract

Berberine (BBR) is a well-known anti-diabetic herbal medicine in Asia due to its beneficial effects on insulin sensitivity, glucose metabolism and glycolysis. Here, we identified the critical role of phosphatidylinositol 3-kinase (PI3K)/Akt involved BBR cellular defense mechanisms and first revealed the novel effect of BBR on nuclear factor (erythroid-derived 2)-related factor-2 (Nrf2)/heme oxygenase (HO)-1 induction in NSC34 motor neuron-like cells. BBR (0.1-10 nM) led to increasing insulin receptor expression, Akt phosphorylation and enhanced oxidant-sensitive Nrf2/HO-1 induction, which were blocked by a PI3K inhibitor, LY294002. In H(2)O(2)-treated cells, BBR significantly attenuated ROS production and increased cell viability, antioxidant defense (GSH and SOD) and oxidant-sensitive proteins (HO-1 and Nrf2), which also were blocked by LY294002. Furthermore, BBR improved mitochondrial function by increasing mitochondrial membrane potential and decreasing the oxygen consumption rate. BBR-induced anti-apoptotic function was demonstrated by increasing anti-apoptotic protein Bcl-2 and survival of motor neuron protein (SMN) and by decreasing apoptotic proteins (cytochrome c, Bax and caspase). These results suggest that BBR, which is active at nanomolar concentration, is a potential neuroprotective agent via PI3K/Akt-dependent cytoprotective and antioxidant pathways.

Berberine activates Nrf2 nuclear translocation and protects against oxidative damage via a phosphatidylinositol 3-kinase/Akt-dependent mechanism in... - PubMed - NCBI