Displacement of corticotropin releasing factor from its binding protein as a possible treatment for Alzheimer's disease

  title={Displacement of corticotropin releasing factor from its binding protein as a possible treatment for Alzheimer's disease},
  author={Dominic P. Behan and Stephen C. Heinrichs and Juan C. Troncoso and Xin-jun Liu and Claudia H. Kawas and Nicholas C. Ling and Errol B. de Souza},
IN Alzheimer's disease (AD) there are dramatic reductions in the content of corticotropin releasing factor (CRF)1–4, reciprocal increases in CRF receptors1,2, and morphological abnormalities in CRF neurons5 in affected brain areas. Cognitive impairment in AD patients is associated with a lower cerebrospinal fluid concentration of CRF6, which is known to induce increases in learning and memory in rodents7–9. This suggests that CRF deficits contribute to cognitive impairment. The identification… 

Corticotropin-releasing factor antagonists, binding-protein and receptors: implications for central nervous system disorders.

A role for CRF binding sites in co-ordinating stress reactivity, emotionality and energy balance over the life-span of the organism is supported.

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

The key evidence for and against the involvement of stress-associated modulation of the CRF system in the pathogenesis of Alzheimer's disease are summarized and how recent findings could lead to new potential treatment possibilities in Alzheimer’s disease by using CRF-BP as a therapeutic target is discussed.

Corticotropin-Releasing Factor (CRF) and Endocrine Responses to Stress: CRF Receptors, Binding Protein, and Related Peptides

  • A. TurnbullC. Rivier
  • Biology
    Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine
  • 1997
Recent findings with respect to CRF, its receptors, binding protein, and CRF-related peptides are described, which provide further insights into the role and mechanisms of CRF action in stress responses.

Corticotropin Releasing Factor Binding Protein as a Novel Target to Restore Brain Homeostasis: Lessons Learned From Alcohol Use Disorder Research

A narrative review focuses on molecular mechanisms related to the role of CRFBP in the progression of addictive and psychiatric disorders, biological aging, and age-related neurodegenerative disease.



Reciprocal changes in corticotropin-releasing factor (CRF)-like immunoreactivity and CRF receptors in cerebral cortex of Alzheimer's disease

In Alzheimer’s, the concentrations of CRF-like immunoreactivity (CRF-IR) are reduced and that there are reciprocal increases in CRF receptor binding in affected cortical areas, which strongly support a neurotransmitter role for CRF in brain and demonstrate, for the first time, a modulation of CNS CRF receptors associated with altered CRF content.

Corticotropin-releasing factor-like immunoreactivity in senile dementia of the Alzheimer type. Reduced cortical and striatal concentrations.

The present findings suggest that neurons containing corticotropin-releasing factor are pathologically altered in SDAT, in addition to the previously described cholinergic and somatostatinergic neuronal degeneration.

Ligand requirements of the human corticotropin-releasing factor-binding protein.

Testing the affinity of recombinant CRF-BP for synthetic analogs of CRF and peptides in the CRF family indicates that residues 9-28 are crucial for ligand binding, and suggests specific pharmacological inhibitors of the ligand-binding protein interaction might be used to therapeutically elevate free CRF levels.

Corticotropin-releasing factor receptors in the rat central nervous system: characterization and regional distribution.

Data from pharmacological studies indicated that the ability of a variety of CRF fragments and analogs to inhibit 125I-rCRF to olfactory bulb membranes correlates well with their reported relative potencies in stimulating pituitary adrenocorticotropic hormone secretion in vitro.

The central distribution of a corticotropin-releasing factor (CRF)-binding protein predicts multiple sites and modes of interaction with CRF.

It is indicated that CRF-BP is expressed predominantly in the cerebral cortex, including all major archi-, paleo-, and neocortical fields, and could serve to modify the actions of CRF by intra- and intercellular mechanisms, inCRF-related pathways in the central nervous system and pituitary.

Reductions in corticotropin releasing factor‐like immunoreactivity in cerebral cortex in Alzheimer's disease, Parkinson's disease, and progressive supranuclear palsy

Reductions in peptidergic immunoreactivity correlated with reductions in the activity of choline acetyltransferase, the enzyme that catalyzes the formation of acetylcholine in the neocortex.

Expression cloning of a human corticotropin-releasing-factor receptor.

The cloning of a cDNA coding for a CRF receptor from a human corticotropic tumor library is reported, which encodes a 415-amino acid protein comprising seven putative membrane-spanning domains and is structurally related to the calcitonin/vasoactive intestinal peptide/growth hormone-releasing hormone subfamily of G protein-coupled receptors.

Immunohistochemical study of neurons containing corticotropin‐releasing factor in Alzheimer's disease

These findings support previous neurochemical studies indicating that certain CRF systems are affected in AD and show that CRF immunoreactivity was markedly increased in some neurons located within the paraventricular nucleus (PVN) of the hypothalamus.

Structure-related effects of CRF and CRF-derived peptides: dissociation of behavioral, endocrine and autonomic activity.

Two C-terminal and one N-Terminal peptide fragments derived from corticotropin-releasing factor (CRF-1-41), CRF-28-41, CRF the most potent fragment, and alpha hCRF were evaluated for their behavioral, endocrine and autonomic nervous effects in rats.