Corticotropin releasing factor-binding protein (CRF-BP) as a potential new therapeutic target in Alzheimer’s disease and stress disorders

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.

Day-night and seasonal variation of human gene expression across tissues

“…POMC expression has been shown to be dependent on longer-term photoperiod in the Siberian hamsters ( 49 ). Other seasonal hormones also have well known roles, mainly in the cardiovascular system and growth: UCN, a corticotropin for stress response and appetite regulation ( 50 , 51 ), NPFF , which controls heart rate and blood pressure ( 52 ), and ADM , which is important for vasodilation ( 53 ). GNRH1 , the gonadotropin-releasing hormone 1, which influences seasonal changes in other mammals ( 54 ), is seasonal in two artery tissues: the aorta and the tibial one.…”

Corticotropin-Releasing Factor Induces Functional And Structural Synaptic Remodelling In Acute Stress

“…Centrally, CRF acts as a neuromodulator of synaptic transmission which can be rapidly and locally released and acts within milliseconds (7) by binding to two different G protein-coupled receptors: CRF-receptor (CRF-R) 1 and 2 (4,7,10). Activation of these receptors can result in a comprehensive array of cellular effects depending on the brain region and the specific CRF-family ligand binding (8,11). This can explain the diversity of responses reported in different brain regions to the same stressor.…”

Modelling and Control of Corticotropin Permeation from Hydrogels across a Natural Membrane in the Presence of Albumin

“…There is growing evidence that ACTH can be used to control corticotropin-releasing factor (CRF) levels, which are affected by Alzheimer's disease (AD), to enhance memory and delay AD progression [7]. ACTH therapy has been shown to delay disease progression and reduce symptoms [8,9].…”