positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of oxidative stress-induced neuron intrinsic apoptotic signaling pathway. [GO_REF:0000058, GOC:bf, GOC:PARL, GOC:TermGenie]

Positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway is a complex process involving a cascade of molecular events that ultimately lead to the programmed death of neurons. This process is triggered by an increase in reactive oxygen species (ROS) levels within neurons, which can result from various stressors, such as environmental toxins, aging, and neurodegenerative diseases.

The initial response to oxidative stress is an attempt to maintain cellular homeostasis and protect against damage. This involves activation of antioxidant defense mechanisms, such as the upregulation of antioxidant enzymes. However, if the stress is severe or prolonged, the cell's ability to cope is overwhelmed, and the apoptotic signaling pathway is initiated.

The intrinsic apoptotic pathway is characterized by the release of pro-apoptotic proteins from the mitochondria into the cytoplasm. This release is regulated by the Bcl-2 family of proteins, which includes both pro- and anti-apoptotic members. Oxidative stress can directly activate pro-apoptotic Bcl-2 proteins, such as Bax and Bak, leading to mitochondrial outer membrane permeabilization (MOMP) and the release of cytochrome c.

Cytochrome c, once in the cytoplasm, binds to the adaptor protein Apaf-1, which then recruits and activates the caspase-9. Caspase-9 is an initiator caspase, which activates downstream executioner caspases, such as caspase-3 and caspase-7. These executioner caspases then cleave a variety of cellular substrates, leading to the dismantling of the cell and its eventual death.

In addition to the Bcl-2 family, other signaling pathways, such as the p53 pathway and the MAPK pathway, are also involved in the regulation of oxidative stress-induced neuronal apoptosis. The p53 pathway is activated by DNA damage and can induce the expression of pro-apoptotic genes. The MAPK pathway can be activated by various stress signals, including oxidative stress, and can promote both pro- and anti-apoptotic responses, depending on the specific MAPKs involved.

The positive regulation of this pathway can be influenced by several factors. For instance, an increase in the expression and activity of pro-apoptotic proteins, such as Bax and Bak, can lead to an acceleration of the apoptotic cascade. Conversely, downregulation of anti-apoptotic proteins, such as Bcl-2, can increase the susceptibility of neurons to apoptosis.

The dysregulation of this pathway is implicated in the pathogenesis of several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. Understanding the molecular mechanisms that regulate oxidative stress-induced neuronal apoptosis is crucial for developing therapeutic strategies to prevent neuronal loss in these conditions.'
"

Proteins (3)

Compounds (117)