Abstract

Protein quality control is essential for the proper function of cells and the organisms that they make up.

The resulting loss of proteostasis, the processes by which the health of the cell's proteins is monitored and maintained at homeostasis, is associated with a wide range of age-related human diseases.

Here, we highlight how the integrated stress response (ISR), a central signaling network that responds to proteostasis defects by tuning protein synthesis rates, impedes the formation of long-term memory.

In addition, we address how dysregulated ISR [Integrated Stress Response] signaling contributes to the pathogenesis of complex diseases, including cognitive disorders, neurodegeneration, cancer, diabetes, and metabolic disorders.

The development of tools through which the ISR can be modulated promises to uncover new avenues to diminish pathologies resulting from it for clinical benefit.

“So what this is doing — is it’s starting to kind of shed light on the specific biological pathways that might be shared across these disorders; namely, these specific neurons that are sort of critical and just brain signaling pathways,” Grotzinger said.

With these findings, Grotzinger hopes to be able to identify what the specific genetic risk pathways are so an individual can be diagnosed and treated more efficiently.

The goal is to be able to give an individual one diagnosis and treatment for the disorders they have instead of multiple, if possible.

Currently, an individual cannot be diagnosed with bipolar and schizophrenia disorder.

However, these two disorders have an overlap in their genetic makeup — meaning that an individual can experience symptoms from both disorders.

Grotzinger hopes in the future diagnoses can be made “a little less sort of by the book.”

In addition, there also may be a possibility of treating certain diagnoses with psychotherapy versus prescription medicines.

The research team only analyzed the genetic variation that showed up in at least 1% of the population“

That really rare stuff might be really important.

And it’s something that we’re just now getting to the point that we can start to look at,”  Grotzinger said.

Researchers are also drastically rethinking theories of how our brains go wrong.

The idea that mental illness can be classified into distinct, discrete categories such as ‘anxiety’ or ‘psychosis’ has been disproved to a large extent*.

Instead, disorders shade into each other, and there are no hard dividing lines — as Plana-Ripoll’s study so clearly demonstrated.