Dorien Vandael1,2,3, Natalia V Gounko4,5,6. 1. VIB-KU Leuven Center for Brain and Disease Research, Electron Microscopy Platform, Herestraat 49, B-3000, Leuven, Belgium. 2. VIB Bioimaging Core Facility, Herestraat 49, B-3000, Leuven, Belgium. 3. KU Leuven Department of Neurosciences, Leuven Brain Institute, Herestraat 49, B-3000, Leuven, Belgium. 4. VIB-KU Leuven Center for Brain and Disease Research, Electron Microscopy Platform, Herestraat 49, B-3000, Leuven, Belgium. natalia.gunko@kuleuven.vib.be. 5. VIB Bioimaging Core Facility, Herestraat 49, B-3000, Leuven, Belgium. natalia.gunko@kuleuven.vib.be. 6. KU Leuven Department of Neurosciences, Leuven Brain Institute, Herestraat 49, B-3000, Leuven, Belgium. natalia.gunko@kuleuven.vib.be.
Abstract
Alzheimer's disease is the most common cause of dementia and one of the most complex human neurodegenerative diseases. Numerous studies have demonstrated a critical role of the environment in the pathogenesis and pathophysiology of the disease, where daily life stress plays an important role. A lot of epigenetic studies have led to the conclusion that chronic stress and stress-related disorders play an important part in the onset of neurodegenerative disorders, and an enormous amount of research yielded valuable discoveries but has so far not led to the development of effective treatment strategies for Alzheimer's disease. Corticotropin-releasing factor (CRF) is one of the major hormones and at the same time a neuropeptide acting in stress response. Deregulation of protein levels of CRF is involved in the pathogenesis of Alzheimer's disease, but little is known about the precise roles of CRF and its binding protein, CRF-BP, in neurodegenerative diseases. In this review, we summarize the key evidence for and against the involvement of stress-associated modulation of the CRF system in the pathogenesis of Alzheimer's disease and discuss how recent findings could lead to new potential treatment possibilities in Alzheimer's disease by using CRF-BP as a therapeutic target.
Alzheimer's disease is the most common cause of n class="Disease">dementia and one of the most complex humanneurodegenerative diseases. Numerous studies have demonstrated a critical role of the environment in the pathogenesis and pathophysiology of the disease, where daily life stress plays an important role. A lot of epigenetic studies have led to the conclusion that chronic stress and stress-related disorders play an important part in the onset of neurodegenerative disorders, and an enormous amount of research yielded valuable discoveries but has so far not led to the development of effective treatment strategies for Alzheimer's disease. Corticotropin-releasing factor (CRF) is one of the major hormones and at the same time a neuropeptide acting in stress response. Deregulation of protein levels of CRF is involved in the pathogenesis of Alzheimer's disease, but little is known about the precise roles of CRF and its binding protein, CRF-BP, in neurodegenerative diseases. In this review, we summarize the key evidence for and against the involvement of stress-associated modulation of the CRF system in the pathogenesis of Alzheimer's disease and discuss how recent findings could lead to new potential treatment possibilities in Alzheimer's disease by using CRF-BP as a therapeutic target.
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