Dear Colleagues,

Disturbed protein homeostasis is associated with several neurodegenerative disorders such as Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and Alzheimer’s disease, among others. In these disorders, there is an accumulation of misfolded proteins in brain cells leading to counterbalancing signaling including the activation of the unfolded protein response in the endoplasmic reticulum (ER) with the aim to restore homeostasis. However, when prolonged or accentuated, ER stress itself is maladaptive and causes defects in protein turnover, calcium and metabolic dysfunctions, increased oxidative stress, and inflammation responses in the brain ultimately leading to cell death. The precise roles of ER stress in the pathogenesis of the neurodegenerative diseases and the mechanisms how ER stress triggers cell death are, however, not fully understood.

In this Special Issue, a collection of papers by distinguished scientists in the field is presented. ER stress will be discussed from different points of view elucidating both its pathophysiology, the signaling mechanisms involved and the possibilities to interfere with and alleviate the consequences of enhanced ER stress in the different diseases. In addition to protein homeostasis, the emerging roles of ER stress in the regulation of RNA and metabolism will also be highlighted. Together, these results underscore the importance of ER stress and its signaling pathways regulating protein homeostasis to meet various challenges that brain cells encounter during normal life, and which contribute to neurodegenerative disorders and brain ageing. An increased understanding of the mechanisms of ER stress and their relationship with other cellular signaling pathways in brain cells and in various neurodegenerative disorders is crucial for the development of better therapies for these diseases.

Prof. Dr. Dan Lindholm
Prof. Dr. Mart Saarma
Dr. Vera Kovaleva
Guest Editors

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• endoplasmic reticulum
• ER stress
• Parkinson’s disease
• Huntington’s disease
• amyotrophic lateral sclerosis
• Alzheimer’s disease
• neurodegenerative disorders