Mitogen-activated protein kinase (MAPK) pathway is one of the most important cell signaling pathways in human brain. Many crucial cellular activities are controlled by the MAPK pathway including cell proliferation, differentiation, and apoptosis. Therefore, it is normally tightly regulated. In the paper we read for this week, the researchers discussed the pathological roles of different kinds of MAPK pathways (ERK, JNK and p38) play in human diseases, including the Alzheimer’s, Parkinson’s, and Amyotrophic lateral sclerosis (ALS). And hopefully by researching into these neurodegenerative diseases, we will be able to eventually find out treatments in order to provide these patients a better quality of life. While oxidative stress is commonly thought to be related to cell death that is associated with both Alzheimer’s and Parkinson’s disease, the risk factors for mutations that are linked to ALS still remain unclear and further investigations are required.
In Alzheimer’s, the reactive oxygen species such as hydroxyl radical, superoxide anion, and hydrogen peroxide cause the oxidative stress and trigger the JNK and p38 signaling pathways. And the activations of these two pathways often lead to cell apoptosis and the formations of senile plaques and neurofibrillary tangles which are generally found in the brains of Alzheimer’s patients and believed to contribute to the disease itself. Although there are no treatments found for Alzheimer’s so far, the researchers are looking into inhibiting the MAPK pathways mentioned above in order to slow the progression of the disease.
Like Alzheimer’s, Parkinson’s disease is another prevalent neurodegenerative disease related to oxidative stress. It is characterized by the accumulation of the Lewy bodies in the brain causing an increasing loss of dopaminergic neurons, and promoting inflammations by activating p38, ERK and JNK pathways. Mutations in multiple genes have been associated with Parkinson’s disease. Although various studies suggest that MAPK pathways contribute to the neuroinflammatory responses and cell apoptosis in Parkinson’s disease, due to its complexity of the pathway, it is very difficult to be diagnosed and cured. An alternative treatment that has been performed on the Parkinson’s patients is called the deep brain stimulation, although it does not cure the disease, it could effectively help the patients manage some of its symptoms.
Amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease is caused by the mutation of the gene which encodes for SOD 1 (Cu/Zn superoxide dismutase) which ultimately results in the death of motor neurons. Although it is unclear how mutations of the SOD 1 gene results in ALS, the researchers believe that the activation of p38 MAPK pathway in motor neurons is important for ALS progression.
Many researches have been done on the neurodegenerative diseases introduced above in order to not only understand but also treat them. Although tons of money and efforts have been put into the studies of the MAPK pathways, due to their complexity, we still have a lot to learn about them. I am certain that life must be very difficult for patients with any of the diseases mentioned in this article, and no one will be able to understand exactly how difficult it is until one gets the disease. Therefore, I believe no matter how difficult to single out one pathway and how complex each pathway is, we should put in more and more resources into researches of these diseases. And eventually, we will be able to cure these patients.