PNAS: By blocking the Bach1 protein, the degeneration of brain cells in Parkinson's disease patients is slowed down

"This is the first evidence that Bach1 is dysregulated in Parkinson's disease," said Dr.

In Parkinson's disease, as the disease progresses, brain cells that produce the chemical messenger dopamine begin to die, leading to tremor and interruption of other motor functions

There are many genes that can fight these destructive pathways, many of which are controlled by two key proteins: Nrf2 and Bach1

Thomas’ laboratory found that the level of Bach1 increased in the brains of PD patients after dissection and in the toxin-based preclinical PD model, indicating that high levels of Bach1 may be related to the pathophysiology of PD

To determine how the loss of Bach1 protects neurons from accumulated stress, they analyzed the entire brain genome of Bach1-deficient mice and observed which genes were activated

Thomas said: "We found that Bach1 not only inhibits the expression of protective genes under the control of Nrf2, but also regulates the expression of many other genes that are not directly controlled by Nrf2

To this end, Thomas collaborated with vTv Therapeutics of North Carolina to develop a Bach1 inhibitor

Therefore, pharmacological intervention using HPPE provides the dual benefits of stabilizing Nrf2 and inhibiting Bach1

The effectiveness of HPPE was tested in a neurotoxin-based PD mouse model

Interestingly, HPPE is more effective than the current FDA-approved Nrf2 activators (such as Tecfidera (dimethyl fumarate)) in protecting neurons

Thomas said: "The most interesting point of this study is that the Bach1 inhibitor is a non-electrophilic agent, so it does not work like the FDA-approved Nrf2 activator

The destruction of Bach1 and the simultaneous activation of Nrf2 clearly provide a strong basis for the use of HPPE as a potential treatment for PD

Thomas said: "When your anti-inflammatory pathway is impaired or mitochondrial dysfunction, this pathway may be beneficial

Journal Reference :

1. Manuj Ahuja, Navneet Ammal Kaidery, Otis C.