Alzheimer’s disease is a neurodegenerative disorder that affects millions of people worldwide. It is a progressive disorder that leads to a decline in cognitive function, memory loss, and eventually, the loss of ability to perform daily tasks. Current research has shown that Alzheimer’s disease is caused by a buildup of abnormal proteins in the brain, known as amyloid-beta and tau. These proteins disrupt the communication between brain cells and ultimately lead to their death.
One of the key pathways involved in the progression of Alzheimer’s disease is the PI3K/AKT pathway. This pathway plays a crucial role in cell survival, growth, and metabolism. It is responsible for regulating various cellular functions, such as cell growth, proliferation, and survival. When this pathway is disrupted, it can contribute to the development and progression of Alzheimer’s disease.
The PI3K/AKT pathway is a signaling pathway that starts with the activation of a protein called PI3K (phosphoinositide 3-kinase). This protein is activated by growth factors and insulin-like growth factors, which are important for cell growth and survival. Once activated, PI3K produces a molecule called PIP3 (phosphatidylinositol 3,4,5-trisphosphate) which then binds to another protein called AKT (also known as protein kinase B).
AKT is a critical player in the PI3K/AKT pathway, and its activation leads to the activation of numerous downstream signaling molecules. These molecules are involved in various cellular processes, including cell growth, proliferation, and survival. One of the key functions of AKT is to promote cell survival by inhibiting cell death pathways.
In Alzheimer’s disease, researchers have found that the PI3K/AKT pathway is dysregulated. This means that there is an imbalance in the activation and inhibition of this pathway, leading to abnormal cell growth and survival. Studies have shown that this imbalance can contribute to the accumulation of toxic proteins, such as amyloid-beta and tau, in the brains of Alzheimer’s patients.
One of the ways in which the PI3K/AKT pathway is affected in Alzheimer’s disease is through the activation of an enzyme called GSK3β (glycogen synthase kinase 3β). GSK3β is a downstream target of AKT and is involved in the regulation of various cellular processes, including cell death. In Alzheimer’s disease, GSK3β becomes overactivated, leading to the phosphorylation of tau protein. This phosphorylation disrupts the normal functioning of tau and leads to its accumulation in the brain, forming neurofibrillary tangles, a characteristic feature of Alzheimer’s disease.
Additionally, the dysregulation of the PI3K/AKT pathway also leads to a decrease in the production of insulin-like growth factors (IGF). IGFs are essential for the survival and growth of brain cells, and their decrease can contribute to the death of neurons. This can ultimately lead to the cognitive decline observed in Alzheimer’s patients.
Furthermore, studies have also shown that oxidative stress, a condition where there is an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to detoxify them, can also affect the PI3K/AKT pathway. ROS can activate GSK3β, leading to further tau phosphorylation and accumulation. Additionally, ROS can also directly damage brain cells, contributing to their death.
In conclusion, the PI3K/AKT pathway plays a crucial role in Alzheimer’s disease progression. Its dysregulation can contribute to abnormal cell growth, survival, and the accumulation of toxic proteins in the brain. Therefore, targeting this pathway may hold promise for developing new treatments for Alzheimer’s disease. Current research is focused on finding ways to regulate the PI3K/AKT pathway to prevent or slow down the progression of this devastating disease.
