Integrated Stress Response

Mechanisms to medicines in neurodegeneration

Dysregulation of protein synthesis both globally and locally in neurons and astrocytes is a key feature of neurodegenerative diseases. Aberrant signalling through the Unfolded Protein Response (UPR) and related Integrated Stress Response (ISR) have become major targets for neuroprotection in these disorders. In addition, other homeostatic mechanisms and stress responses, including the cold shock response, appear to regulate local translation and RNA splicing to control synapse maintenance and regeneration and can also be targeted therapeutically for neuroprotection. We have defined the role of UPR/ISR and the cold-shock response in neurodegenerative disorders and have developed translational strategies targeting them for new treatments for dementia.

Aberrant cortical spine dynamics after concussive injury are reversed by integrated stress response inhibition

FUS-mutation carrying amyotrophic lateral sclerosis patient-derived motoneurons display lower survival, accumulate more DNA damage, and show elevated integrated stress response

FENS Forum 2024

Neurons repurpose the integrated stress response effector GADD34 to enhance protein synthesis in response to neuronal activity

FENS Forum 2024